Born into an aristocratic family, Lyndsay was appointed attendant and companion to the infant prince (born 1512), the son of King James IV. Dismissed from court 12 years later, when his charge, then James V, fell under the control of the Douglas faction, he returned to the king's service in 1528. An influential diplomat, Lyndsay represented the king on important missions to the courts of Henry VIII, Charles V, Francis I (after James's death in 1542), and other European monarchs. Most of his verse, with a work on heraldry, was written during his prosperous years at court.

Lyndsay's Ane Satyre of the Thrie Estaits is the only surviving complete Scottish morality play. Originally entitled “the mysdemeanours of Busshops Religious persones and preists within the Realme” (1540), it was enlarged with coarse comedy and performed in 1552 at Cupar, Fife, and again on the slopes of the Calton Hill, Edinburgh. It is a dramatic representation of the crucial issues of the midcentury in religion, government, and social life, with all classes of society mirrored, admonished, and entertained.

The Dreme (completed 1528), Lyndsay's earliest surviving work in verse, is an allegory of the contemporary condition of Scotland, with a delightfully personal epistle to the king. The Testament and Complaynt of Our Soverane Lordis Papyngo (completed 1530), written to celebrate the king's escape from the Douglases, is a mixture of satire, comedy, and moral instruction in which the king's dying parrot gives advice to the king and court; and his An Answer quhilk Schir David Lyndsay maid to the Kingis Flyting (1536) is a ribald example of the game of poetic abuse (“flyting”) practiced by Celtic poets. The Complaynt and Publict Confessioun of the Kingis Auld Hound callit Bagsche (c. 1536) is a short didactic piece, satirizing court life through the mouth of a dog, a device later revived by Robert Burns.