Spooner was born on a farm in Athol, Massachusetts, on January 19, 1808, and died "at one o'clock in the afternoon of Saturday, May 14, 1887, in his little room at 109 Myrtle Street, [Boston,] surrounded by trunks and chests bursting with the books, manuscripts, and pamphlets which he had gathered in his active pamphleteer's warfare over half a century long."

Spooner advocated what he called Natural Law – or the "Science of Justice" – wherein acts of initiatory coercion against individuals and their property were considered "illegal" but the so-called criminal acts that violated only man made legislation were not.

His activism began with his career as a lawyer, which itself violated Massachusetts law. Spooner had studied law under the prominent lawyers and politicians John Davis and Charles Allen, but he had never attended college. According to the laws of the state, college graduates were required to study with an attorney for three years, while non-graduates were required to do so for five years. With the encouragement of his legal mentors, Spooner set up his practice in Worcester after only three years, openly defying the courts. He saw the three year privilege for college graduates as a state sponsored discrimination against the poor and also providing a monopoly income to those who met the requirements. He argued that "no one has yet ever dared advocate, in direct terms, so monstrous a principle as that the rich ought to be protected by law from the competition of the poor." In 1836, the legislature abolished the restriction. He opposed all licensing requirements for lawyers, doctors or anyone else that was prevented from being employed by such requirements. To prevent a person from doing business with a person without a professional license he saw as a violation of the natural right to contract.

After a disappointing legal career - his radical writing seems to have kept away potential clients - and a failed career in real estate speculation in Ohio, Spooner returned to his father's farm in 1840.

Being an advocate of self-employment and opponent of government regulation of business, Spooner started his own business called American Letter Mail Company which competed with the U.S. Post Office. Postal rates were notoriously high in the 1840s, and in 1844, Spooner founded the American Letter Mail Company, which had offices in various cities, including Baltimore, Philadelphia, and New York. Stamps could be purchased and then attached to letters which could be sent to any of its offices. From here agents were dispatched who traveled on railroads and steamboats, and carried the letters in hand bags. Letters were transferred to messengers in the cities along the routes who then delivered the letters to the addressees. This was a challenge to the United States Post Office's monopoly. As he had done when challenging the rules of the Massachusetts bar, he published a pamphlet titled "The Unconstitutionality of the Laws of Congress Prohibiting Private Mails." Although Spooner had finally found commercial success with his mail company, legal challenges by the government eventually exhausted his financial resources. He closed up shop without ever having had the opportunity to fully litigate his constitutional claims. The lasting legacy of Spooner's challenge to the postal service was the 3 cent stamp, adopted in response to the competition his company provided.

Spooner challenged the claim that the text of the Constitution supported slavery. Although he recognized that the Founders had probably not intended to outlaw slavery when writing the Constitution, he argued that only the meaning of the text, not the private intentions of its writers, was enforceable. Spooner used a complex system of legal and natural law arguments in order to show that the clauses usually interpreted as supporting slavery did not, in fact, support it, and that several clauses of the Constitution prohibited the states from establishing slavery under the law. Spooner's arguments were cited by other pro-Constitution abolitionists, such as Gerrit Smith and the Liberty Party, which adopted it as an official text in its 1848 platform. Frederick Douglass, originally a Garrisonian disunionist, later came to accept the pro-Constitution position, and cited Spooner's arguments to explain his change of mind.

From the publication of this book until 1861, Spooner actively campaigned against slavery. He published subsequent pamphlets on Jury Nullification and other legal defenses for escaped slaves and offered his legal services, often free of charge, to fugitives. In the late 1850s, copies of his book were distributed to members of Congress sparking some debate over their contents. Even Senator Albert Gallatin Brown of Mississippi, a slavery proponent, praised the argument's intellectual rigor and conceded it was the most formidable legal challenge he had seen from the abolitionists to date. In 1858, Spooner circulated a "Plan for the Abolition of Slavery," calling for the use of guerrilla warfare against slaveholders by black slaves and non-slaveholding free Southerners, with aid from Northern abolitionists. Spooner also "conspir[ed] with John Brown to promote a servile insurrection in the South," and participated in an aborted plot to free Brown after his capture following the failed raid on Harper's Ferry, Virginia (Harper's Ferry is now part of the state of West Virginia).

In 1860, Spooner was actively courted by William Seward to support the fledgling Republican Party. An admitted sympathizer with the Jeffersonian political philosophy, Spooner adamantly refused the request and soon became an outspoken abolitionist critic of the party. To Spooner, the Republicans were hypocrites for purporting to oppose slavery's expansion but refusing to take a strong, consistent moral stance against slavery itself. Although Spooner had advocated the use of violence to abolish slavery, he denounced the Republicans' use of violence to prevent the Southern states from seceding during the American Civil War. He published several letters and pamphlets about the war, arguing that the Republican objective was not to eradicate slavery, but rather to preserve the Union by force. He blamed the bloodshed on Republican political leaders, such as Secretary of State William H. Seward and Senator Charles Sumner, who often spoke out against slavery but would not attack it on a constitutional basis, and who pursued military policies seen as vengeful and abusive.

Although he denounced the institution of slavery, Spooner recognized the right of the Confederate States of America to secede as the manifestation of government by consent, a constitutional and legal principle fundamental to Spooner's philosophy; the Northern states, in contrast, were trying to deny the Southerners that right through military force. He "vociferously opposed the Civil War, arguing that it violated the right of the southern states to secede from a Union that no longer represented them." He believed they were attempting to restore the Southern states to the Union, against the wishes of Southerners. He argued that the right of the states to secede derives from the natural right of slaves to be free. This argument was unpopular in the North and in the South after the War began, as it conflicted with the official position of both governments.

As a means to end slavery without bloodshed, Spooner offered compensated emancipation, a method tested and proven in those nations that had orchestrated the peaceful abolition of slavery.

Spooner believed that government restrictions on issuance of private money made it inordinately difficult for individuals to obtain the capital on credit to start their own businesses, thereby putting them in a situation where "a very large portion of them, to save themselves from starvation, have no alternative but to sell their labor to others" and those who do employ others are only able afford to pay "far below what the laborers could produce, [than] if they themselves had the necessary capital to work with." Spooner said that there was "a prohibitory tax --- a tax of ten per cent. --- on all notes issued for circulation as money, other than the notes of the United States and the national banks" which he argued caused an artificial shortage of credit, and that eliminating this tax would result in making plenty of money available for lending such that: "All the great establishments, of every kind, now in the hands of a few proprietors, but employing a great number of wage labourers, would be broken up; for few or no persons, who could hire capital and do business for themselves would consent to labour for wages for another."

Economist Murray Rothbard, in 1974, argued against Spooner's theory. Though agreeing that government should not have any regulations on money, he argued that "an increase in the supply of money does not confer any benefit whatever on society" but simply dilutes the purchasing power. Moreover, Rothbard said that in an anarchist society, the quantity of money would actually not increase as Spooner theorizes, but that supply would be even more limited than when governments and central banks manage the money supply, and fortunately so.

Spooner harshly condemned the American Civil War and the Reconstruction period that followed. Though he approved of the abolition of black slavery, he criticized the North for failing to make this the purpose of their cause. Instead of fighting to abolish slavery, they fought to "preserve the union" and, according to Spooner, to bolster business interests behind that union. Spooner believed a war of this type was hypocritical and dishonest, especially on the part of Radical Republicans like Sumner who were by then claiming to be abolitionist heroes for ending slavery. Spooner also argued that the war came at a great cost to liberty and proved that the rights expressed in the Declaration of Independence no longer held true - the people could not "dissolve the political bands" that tie them to a government that "becomes destructive" of the consent of the governed because if they did so, as Spooner believed the South had attempted to do, they would be met by the bayonet to enforce their obedience to the former government.

The Union government's actions during the war caused Spooner to radicalize his views to an anarchistic view. In response, Spooner published a series of political tracts, No Treason. The most famous of these is No Treason No. VI: The Constitution of No Authority. In this lengthy essay, Spooner argued that the Constitution was a contract of government (social contract theory) which could not logically apply to anyone other than the individuals who signed it, and was thus void. Furthermore, since the government now existing under the Constitution pursued coercive policies that were contrary to the Natural Law and to the consent of the governed, it had been demonstrated that that document could not adequately stop many abuses against liberty or prevent tyranny from taking hold. Spooner bolstered his argument by noting that the federal government, as established by a legal contract, could not legally bind all persons living in the nation since none had ever signed their names or given their consent to it - that consent had always been assumed, which fails one of the most basic burdens of proof for a valid contract in the courtroom.

Spooner widely circulated the No Treason pamphlets, which also contained a legal defense against the crime of treason itself intended for former Confederate soldiers (hence the name of the pamphlet, arguing that "no treason" had been committed in the war by the South). These excerpts were published in DeBow's Review and in some other well known southern periodicals of the time.

George Woodcock describes Spooner's essays as an "eloquent elaboration" of Josiah Warren and the early American development of Proudhon's ideas, and associates his works with that of Stephen Pearl Andrews.

Spooner became a member of the socialist First International. Spooner continued to write and publish extensively in the decades following Reconstruction, producing works such as "Natural Law or The Science of Justice" and "Trial By Jury." In "Trial By Jury" he defended the doctrine of "Jury Nullification", which holds that in a free society a trial jury not only has the authority to rule on the facts of the case, but also on the legitimacy of the law under which the case is tried, and which would allow juries to refuse to convict if they regard the law they are asked to convict under as illegitimate. He became closely associated with Benjamin Tucker's anarchist journal Liberty, which published all of his later works in serial format, and for which he wrote several editorial columns on current events. He argued that ". . . almost all fortunes are made out of the capital and labour of other men than those who realise them. Indeed, except by his sponging capital and labour from others."

Spooner died on May 14, 1887 at the age of 79 in his residence, 109 Myrtle Street, Boston. Benjamin Tucker arranged his funeral service and wrote a "loving obituary," entitled "Our Nestor Taken From Us," which appeared in Liberty on May 28, and predicted "that the name Lysander Spooner would be 'henceforth memorable among men.'"

Spooner's influence extends to the wide range of topics he addressed during his lifetime. He is remembered today primarily for his abolitionist activities and for his challenge to the post office monopoly, which had a lasting influence of significantly reducing postal rates. Spooner's writings contributed to the development of libertarian political theory in the United States, and were often reprinted in early libertarian journals such as the Rampart Journal and Left and Right: A Journal of Libertarian Thought. His writings were also a major influence on Austrian School economist Murray Rothbard and libertarian law professor and legal theorist Randy Barnett.

In January 2004, Laissez Faire Books established the Lysander Spooner Award for advancing the literature of liberty. The honor is awarded monthly to the most important contributions to the literature of liberty, followed by an annual award to the author of the top book on liberty for the year. The annual "Spooner" earns $1,500 cash for the winning author. Conversely, proponents of market socialism cite Spooner for his opposition to wage labor.

Spooner's The Unconstitutionality of Slavery was cited in the 2008 District of Columbia v. Heller Supreme Court case which struck down the federal district's ban on handguns. Justice Antonin Scalia, writing for the court, quotes Spooner as saying the right to bear arms was necessary for those who wanted to take a stand against slavery. It was also cited by Justice Clarence Thomas in his concurring opinion in McDonald v. Chicago the following year.