Burton spent most of his life at Oxford, where he was a fellow of Brasenose College. He studied a large number of diverse subjects, many of which made their way into the study of melancholia for which he is chiefly famous. He was appointed vicar of St. Thomas Church in Oxford in 1616, and in 1630 he was also made the rector of Segrave, Leicester. Apart from The Anatomy of Melancholy his only other published work is Philosophaster, a satirical Latin comedy.
He wrote The Anatomy of Melancholy largely because he found himself a lifelong suffer from melancholia. As he put it,