About 1726 Baskerville became a writing master at Birmingham, and he seems to have had a great talent for calligraphy and for cutting inscriptions in stone. While at Birmingham he made some important improvements in the process of japanning, and gained a considerable fortune. About the year 1750 he began to make experiments in type-founding, producing types much superior in distinctness and elegance to any that had hitherto been employed. He set up a printing-house, and in 1757 published his first work, a Virgil in royal quarto, followed, in 1758, by his famous edition of Milton. In that year he was appointed printer to the university of Cambridge, and undertook editions of the Bible and the Book of Common Prayer. The Horace, published in 1762, is distinguished even among the productions of the Baskerville press for its correctness and for the beauty of the paper and type. A second Horace appeared in 1770 in quarto, and its success encouraged Baskerville to publish a series of quarto editions of Latin authors, which included Catullus, Tibullus, Propertius, Lucretius, Terence, Sallust and Florus. This list of books issued by Baskerville from his press lends some irony to the allegation that he was a person of no education. These books are admirable specimens of typography; and Baskerville is deservedly ranked among the foremost of those who have advanced the art of printing. His contemporaries asserted that his books owed more to the quality of the paper and ink than to the type itself, but the difficulty in obtaining specimens from the Baskerville press shows the estimation in which they are now held. His wife carried on the business for some time after his death, which took place on the 8th of January 1775.
Baskerville was a member of the Royal Society of Arts, and an associate of some of the members of the Lunar Society.
Baskerville was married to Sarah Eaves.