According to his son, he was born at Santon Hall, Norfolk, and educated at Bury St Edmunds School, and at Caius College, Cambridge, which he was entered in 1656. He left the university without a degree, and joined the Middle Temple. In 1668 he produced a prose comedy, The Sullen Lovers, or the Impertinents, based on Les Fâcheux by Molière, and written in open imitation of Ben Jonson. His best plays are Epsom Wells (1672), for which Sir Charles Sedley wrote a prologue, and the Squire of Alsatia (1688). Alsatia was the cant name for Whitefriars, then a kind of sanctuary for persons liable to arrest, and the play represents, in dialogue full of the local argot, the adventures of a young heir who falls into the hand of the sharpers there.
For fourteen years from the production of his first comedy to his memorable encounter with John Dryden, Shadwell produced a play nearly every year. These productions display a hatred of sham, and a rough but honest moral purpose. Although bawdy, they present a vivid picture of contemporary manners. Shadwell is chiefly remembered as the unfortunate Mac Flecknoe of Dryden's satire, the "last great prophet of tautology," and the literary son and heir of Richard Flecknoe:
"The rest to some faint meaning make pretence,
But Shadwell never deviates into sense."
Dryden had furnished Shadwell with a prologue to his True Widow (1679), and in spite of momentary differences, the two had been on friendly terms. But when Dryden joined the court party, and produced Absalom and Achitophel and The Medal, Shadwell became the champion of the Protestants, and made a scurrilous attack on Dryden in The Medal of John Bayes: a Satire against Folly and Knavery (1682). Dryden immediately retorted in Mac Flecknoe, or a Satire on the True Blue Protestant Poet, T.S. (1682), in which Shadwell's personalities were returned with interest. A month later he contributed to Nahum Tate's continuation of Absalom and Achitophel satirical portraits of Elkanah Settle as Doeg and of Shadwell as Og. In 1687 Shadwell attempted to answer these attacks in a version of the tenth satire of Juvenal. At the Whig triumph in 1688 he superseded his enemy as Poet Laureate and historiographer royal. He died at Chelsea.
His son, Charles Shadwell was also a playwright.
A complete edition of Shadwell's works was published by another son, Sir John Shadwell, in 1720. His other dramatic works are: