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's comedy of humours. 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 the Whitefriars area of London, 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 hands 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 pretense, But Sh____ 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 Juvenal's 10th Satire.
However, Dryden's portrait of Shadwell in Absalom and Achitophel cut far deeper, and has withstood the test of time. In this satire, Dryden noted of Settle and Shadwell:
Two fools that crutch their feeble sense on verse; Who, by my muse, to all succeeding times Shall live, in spite of their own doggrel rhymes;
Nonetheless, Shadwell, due to the Whig triumph in 1688 superseded his enemy as Poet Laureate and historiographer royal.
His son, Charles Shadwell was also a playwright. A scene from his play, "The Stockjobbers" was included as an introduction in Caryl Churchill's "Serious Money" (1987).