John Hanson, Jr. was born at "Mulberry Grove" in Port Tobacco Parish in Charles County in the British Province of Maryland. The American National Biography lists Hanson's birth date as April 3, 1721, which in the modern calendar system is equivalent to April 14, although the older Dictionary of American Biography gives the date as April 13, 1721. Some older sources list a birth year of 1715. Hanson's parents were Samuel and Elizabeth (Story) Hanson. Samuel Hanson was a planter who owned more than 1,000 acres (4.0 km²), and held a variety of political offices, including serving two terms in the Maryland General Assembly. John Hanson was of English ancestry; his grandfather, also named John, came to Charles County, Maryland, as an indentured servant around 1661. In 1876, a writer named George Hanson placed John Hanson in his family tree of Swedish Americans descended from four Swedish brothers who emigrated to New Sweden in 1642. This story was often repeated over the next century, but scholarly research in the late 20th century suggested that John Hanson was of English heritage and not related to these Swedish American Hansons.

Hanson had no extended formal education while growing up in Maryland, but he read broadly in both English and Latin. He followed the family tradition as a planter, extending and improving his holdings. About 1744 he married Jane Contee, with whom he would have eight children. Their son Alexander Contee Hanson, Sr. (1749 – 1806) was a notable essayist. Alexander Hanson is sometimes confused with his son, Alexander Contee Hanson, Jr., who became a newspaper editor and US Senator.

Hanson's career in public service began in 1750, when he was appointed sheriff of Charles County. In 1757 he was elected to represent Charles County in the lower house of the Maryland General Assembly, where he served over the next twelve years, sitting on many important committees. Maryland was a proprietary colony, and Hanson aligned himself with the "popular" or "country" party, which opposed any expansion of the power of the proprietary governors at the expense of the popularly elected lower house. He was a leading opponent of the 1765 Stamp Act, chairing the committee that drafted the instructions for Maryland's delegates to the Stamp Act Congress. In protest of the Townshend Acts, in 1769 Hanson was one of the signers of a nonimportation resolution that boycotted British imports until the acts were repealed.

Hanson changed course in 1769, apparently to better pursue his business interests. He resigned from the General Assembly, sold his land in Charles County, and moved to Frederick County in western Maryland. There he held a variety of offices, including deputy surveyor, sheriff, and county treasurer.

When relations between Great Britain and the colonies became a crisis in 1774, Hanson became one of Frederick County's leading Patriots. He chaired a town meeting that passed a resolution opposing the Boston Port Act. In 1775, he was a delegate to the Maryland Convention, an extralegal body convened after the colonial assembly had been prorogued. With the other delegates, he signed the Association of Freemen on July 26, 1775, which expressed hope for reconciliation with Great Britain, but also called for military resistance to enforcement of the Coercive Acts.

With hostilities underway, Hanson chaired the Frederick County committee of observation, part of the Patriot organization that assumed control of local governance. Responsible for recruiting and arming soldiers, Hanson proved to be an excellent organizer, and Frederick County sent the first southern troops to join George Washington's army.

Hanson was elected to the newly reformed Maryland House of Delegates in 1777, the first of five annual terms. In December 1779, the House of Delegates named Hanson as one of its delegates to the Second Continental Congress. He began those duties when he took his seat in Philadelphia on June 14, 1780, serving until 1782. While Hanson was in Congress, the Articles of Confederation were at last ratified by all the states. When the Congress received notice of this on March 1, 1781, he joined Daniel Carroll in endorsing them for Maryland.

In November 1781, Hanson became the first President of Congress to be elected for an annual term as specified in the Articles of Confederation, although Samuel Huntington and Thomas McKean had served in that office after the ratification of the Articles. Under the Articles of Confederation, the United States had no executive branch; the President of Congress was a mostly ceremonial position within the Confederation Congress, but the office did require Hanson to handle a good deal of correspondence and sign official documents. Hanson found the work tedious and wished to resign, but his departure would have left Congress without a quorum to select a successor, and so, out of a sense of duty, he remained in office.

Because Hanson was the first president under the Articles of Confederation, one of his grandsons later promoted him as the first President of the United States. This ultimately resulted in Hanson's statue being one of two representing Maryland in Statuary Hall in the U.S. Capitol, even though, according to historian Gregory Stiverson, Hanson was not one of Maryland's foremost leaders of the Revolutionary era. The claim that Hanson was the forgotten first President of the United States was further promoted in an 1932 biography of Hanson by journalist Seymour Wemyss Smith. Smith's book, which contained no footnotes or references, made expansive claims about Hanson's role, asserting that the American Revolution had two primary leaders: George Washington in the military sphere, and John Hanson in politics.

Hanson retired from public office after his one-year term as President of Congress. In poor health, he died a year later at his nephew's plantation Oxon Hill Manor in Prince George's County, Maryland, on November 22, 1783. The grave site is lost.

Maryland law specifies that "the Governor annually shall proclaim April 13 as John Hanson's birthday and dedicate that day to the statesman." Also, the John Hanson Highway is named in his honor. There are also middle schools located in Oxon Hill, Maryland, and Waldorf, Maryland, named after him. A former savings bank named for him was merged in the 1990s with Industrial Bank of Washington, DC. A namesake, John Hanson Briscoe, was a circuit judge and Speaker of the Maryland House of Delegates.

In 1903 the state of Maryland donated a bronze statue by Richard E. Brooks to the United States Capitol's National Statuary Hall Collection. It is currently located on the 2nd floor of the Senate connecting corridor. A maquette of the Hanson statue by Brooks resides on the President's dais in the Senate Chamber of the Maryland State House.