He was born at the Chateau de la Brede in the southwest of France. After having studied at the Catholic College of Juilly, Charles-Louis de Secondat married. His wife, Jeanne de Lartigue, a Protestant, brought him a substantial dowry when he was 26. The next year, he inherited a fortune upon the death of his uncle, as well as the title Baron de Montesquieu and Président à Mortier in the Parliament of Bordeaux. By that time, England had declared itself a constitutional monarchy in the wake of its Glorious Revolution (1688–89), and had joined with Scotland in the Union of 1707 to form the Kingdom of Great Britain. In 1715 the long-reigning Louis XIV died and was succeeded by the five-year-old Louis XV. These national transformations impacted Montesquieu greatly; he would later refer to them repeatedly in his work.

Soon afterwards he achieved literary success with the publication of his Lettres persanes (Persian Letters, 1721), a satire based on the imaginary correspondence of a Persian visitor to Paris, pointing out the absurdities of contemporary society. He next published Considérations sur les causes de la grandeur des Romains et de leur décadence (Considerations on the Causes of the Grandeur and Decadence of the Romans, 1734), considered by some scholars a transition from The Persian Letters to his master work. De l'Esprit des Lois (The Spirit of the Laws) was originally published anonymously in 1748 and quickly rose to a position of enormous influence. In France, it met with an unfriendly reception from both supporters and opponents of the regime. The Catholic Church banned l'Esprit – along with many of Montesquieu's other works – in 1751 and included it on the Index of Prohibited Books. It received the highest praise from the rest of Europe, especially Britain.

Montesquieu was also highly regarded in the British colonies in America as a champion of British liberty (though not of American independence). Political scientist Donald Lutz found that Montesquieu was the most frequently quoted authority on government and politics in colonial pre-revolutionary British America. Following the American secession, Montesquieu's work remained a powerful influence on many of the American founders, most notably James Madison of Virginia, the "Father of the Constitution". Montesquieu's philosophy that "government should be set up so that no man need be afraid of another" reminded Madison and others that a free and stable foundation for their new national government required a clearly defined and balanced separation of powers.

Besides composing additional works on society and politics, Montesquieu traveled for a number of years through Europe including Austria and Hungary, spending a year in Italy and 18 months in England before resettling in France. He was troubled by poor eyesight, and was completely blind by the time he died from a high fever in 1755. He was buried in the Église Saint-Sulpice, Paris.

Montesquieu is credited amongst the precursors of anthropology, including Herodotus and Tacitus, to be among the first to extend comparative methods of classification to the political forms in human societies. Indeed, the French political anthropologist Georges Balandier considered Montesquieu to be "the initiator of a scientific enterprise that for a time performed the role of cultural and social anthropology". According to social anthropologist D.F. Pocock, Montesquieu's 'Spirit of the Laws' "is the first consistent attempt to survey the varieties of human society, to classify and compare them and, within society, to study the inter-functioning of institutions". Montesquieu's political anthropology gave rise to his theories on government.

Montesquieu's most influential work divided French society into three classes (or trias politica, a term he coined): the monarchy, the aristocracy, and the commons. Montesquieu saw two types of governmental power existing: the sovereign and the administrative. The administrative powers were the executive, the legislative, and the judicial. These should be separate from and dependent upon each other so that the influence of any one power would not be able to exceed that of the other two, either singly or in combination. This was radical because it completely eliminated the three Estates structure of the French Monarchy: the clergy, the aristocracy, and the people at large represented by the Estates-General, thereby erasing the last vestige of a feudalistic structure.

Likewise, there were three main forms of government, each supported by a social "principle": monarchies (free governments headed by a hereditary figure, e.g. king, queen, emperor), which rely on the principle of honor; republics (free governments headed by popularly elected leaders), which rely on the principle of virtue; and despotisms (enslaved governments headed by dictators), which rely on fear. The free governments are dependent on fragile constitutional arrangements. Montesquieu devotes four chapters of The Spirit of the Laws to a discussion of England, a contemporary free government, where liberty was sustained by a balance of powers. Montesquieu worried that in France the intermediate powers (i.e., the nobility) which moderated the power of the prince were being eroded. These ideas of the control of power were often used in the thinking of Maximilien de Robespierre.

Montesquieu was somewhat ahead of his time in advocating major reform of slavery in The Spirit of the Laws. As part of his advocacy he presented a satirical hypothetical list of arguments for slavery, which has been open to contextomy. However, like many of his generation, Montesquieu also held a number of views that might today be judged controversial. He firmly accepted the role of a hereditary aristocracy and the value of primogeniture, and while he endorsed the idea that a woman could head a government, he held that she could not be effective as the head of a family.

Another example of Montesquieu's anthropological thinking, outlined in The Spirit of the Laws and hinted at in Persian Letters, is his meteorological climate theory, which holds that climate may substantially influence the nature of man and his society. By placing an emphasis on environmental influences as a material condition of life, Montesquieu prefigured modern anthropology's concern with the impact of material conditions, such as available energy sources, organized production systems, and technologies, on the growth of complex socio-cultural systems. He goes so far as to assert that certain climates are superior to others, the temperate climate of France being ideal. His view is that people living in very warm countries are "too hot-tempered," while those in northern countries are "icy" or "stiff." The climate of middle Europe is therefore optimal. On this point, Montesquieu may well have been influenced by a similar pronouncement in The Histories of Herodotus, where he makes a distinction between the 'ideal' temperate climate of Greece as opposed to the overly cold climate of Scythia and the overly warm climate of Egypt. This was a common belief at the time, and can also be found within the medical writings of Herodotus' times, including the 'On Airs, Waters, Places' of the Hippocratic corpus. One can find a similar statement in Germania by Tacitus, one of Montesquieu's favorite authors. However, the earlier works that most closely resemble Montesquieu's complex climiate theory are the Muqaddimah (1377) by the Arab sociologist, Ibn Khaldun, and The Travels of Sir John Chardin in Persia and the Orient (1711) by the French traveller Jean Chardin. From a sociological perspective Louis Althusser, in his analysis of Montesquieu's revolution in method, alluded to the seminal character of anthropology's inclusion of material factors, such as climate, in the explanation of social dynamics and political forms. Examples of certain climatic and geographical factors giving rise to increasingly complex social systems include those that were conducive to the rise of agriculture and the domestication of wild plants and animals.