Crawford was born in Amherst County, Virginia, but his family moved south to Appling County, Georgia when he was a boy. As a young man, he worked as a farmer and a schoolteacher for about 10 years, then began to practice law in Lexington, Georgia in 1799.

In 1803, Crawford was elected to the Georgia state legislature as a member of the Democratic-Republican Party. In 1807, that legislature elected him to fill a vacant United States Senate seat.

Crawford soon became a respected and influential senator, and was elected president pro tempore in 1811. In recognition of his abilities, President James Madison appointed Crawford as the American minister to the First French Empire in 1812. Crawford held that important ministerial post throughout the War of 1812, and returned shortly after its end in 1815.

Upon Crawford's return, Madison appointed him as Secretary of War. After slightly more than a year of satisfactory service in that post (and after disclaiming interest in the 1816 Democratic-Republican nomination for President, which he could have had), Crawford moved within the Cabinet to become Secretary of the Treasury.

Crawford was again a leading candidate for the Democratic-Republican presidential nomination in 1824, but a massive stroke in 1823 ended his chances. The Democratic-Republican Party split apart that year, and one of the splinter groups nominated Crawford. Despite Crawford's improved health (and the support of former presidents Madison and Thomas Jefferson), he finished only third, behind John Quincy Adams and Andrew Jackson. Refusing Adams' request that he remain at the Treasury, Crawford then retired to Georgia, where he was appointed as a state superior court judge.

Crawford remained an active judge until his death a decade later. He is buried in Crawford Cemetery in Crawford, Georgia.