The main source of information on Centlivre's early life is Giles Jacob, who claimed that he had the information from her directly (Poetical Register of 1719). She was born in Holbeach, near Spalding, Lincolnshire in 1667 Famous People from Spalding Her father, William Freeman, was a dissenter in Ireland, and her mother's name was Anne. William was apparently abusive, and, after the English Restoration, certainly impoverished, and Susanna ran away from home. Abel Boyer, a Whig historian who published Centlivre's early writing, corroborates some of Jacob's account, but suggests that Centlivre may have been orphaned.

She married a man named Fox, supposedly the nephew of Sir Stephen Fox, when she was fifteen or sixteen years old. According to Jacob, he died within a year. The marriage to Fox has been corroborated, but the circumstances of the marriages have not. Nevertheless, she was apparently a widow by age seventeen. She then married an army officer named Caroll or Carroll who died within a year and a half of their wedding, possibly in a duel.She retained the surname Carroll and used it during the early part of her career.

How she arrived at the theatre is a matter of confusion. Jacob's account has her meeting with some strolling players and being struck by the gaiety and quality of drama. Another account suggests that Carroll was a seducer who led her to the theatre. Another places her at Cambridge studying dressed as a boy after which she ended up in London writing plays. At any rate, she began acting in breeches roles and writing plays and signing them "Susanna Carroll."

In 1700, she contributed poetry to The Nine Muses, an elegiac poetry collection left on the grave of John Dryden. She had moved over to Drury Lane in London by that year, and her first play, The Perjured Husband, appeared. As with other plays of that year, it was a combination of tragedy with a sexually titillating subplot (cf. the plays of John Vanbrugh and Colley Cibber). The play was a great success, and the prologue explicitly boasted that it had been written by a woman.

She was a prolific and always busy author and actress thereafter. In 1702, she wrote and had produced both The Beau Duel and The Stolen Heiress, with Love's Contrivance the next season. In 1705, she wrote The Gamester and The Basset Table. She was a friend at that point of George Farquhar, William Burnaby, Nicholas Rowe, Colley Cibber, Ambrose Philips, Thomas Baker, Thomas Burnet, and Richard Steele, and she contributed prologues to their plays, while they contributed to hers. The Gamester and The Basset Table were great theatrical successes, and the author appears to have moved in the highest literary and political circles. In addition to these plays, she was also acting.

In 1706, she wrote Love at a Venture (continuing with her gaming theme), and Colley Cibber rejected the play as too bawdy. However, he plagiarized the play for his own The Double Gallant. The next year, she wrote The Platonick Lady, and the preface to the printed play denounced the sexism [the use of this word here is anachronistic, since the concept of "sexism" didn't exist at the time - "prejudice" would be a more appropriate term, being current in the 18th century] that led to any work by a woman being judged as inherently inferior to a work by a man. While she was playing the breeches part of Alexander in Nathaniel Lee's The Rival Queens at a benefit for Queen Anne, she met Joseph Centlivre, one of the cooks for the queen. The two were married in April, 1707.

In 1709, she had one of her greatest successes with The Busybody. The play ran for thirteen nights, which was a remarkable run for the time, and was revived the following season. In it, the character Marplot brings utter confusion to a series of couples who are attempting to woo. His well-intentioned efforts nearly derail all the romance. The play had over 450 performances by 1800, and went through 40 editions by 1884, and George I and George II both commanded performances be done. Additionally, Marplot was one of David Garrick's favorite roles. The sequel to The Busybody, Marplot in Lisbon, was however not much of a success.

Also in 1709, she wrote The Man's Bewitched, a play satirizing the squirearchy of Tory gentlemen in the country. This political satire took part in an ongoing election struggle, and the Tory press struck back. The weekly journal The Female Tatler printed an "interview" that it had done with Centlivre, where she insulted the actors and blamed them for all her failures. The company was on the verge of walking out on her, and she had to convince them that she was the victim of a political fight and a hoax.

In 1712, two years before the death of Anne and at a time when both parties were making secret overtures to the Old Pretender, Centlivre took an explicit pro-Hanoverian position in public. In 1714, when Anne died and the Hanoverians were invited to the throne, she bragged of her foresight and acumen with A Woman's Case, a poem, and dedicated her play The Wonder: A Woman Keeps a Secret to George I. In 1715, a year of Jacobite uprising and a Parliamentary election, she wrote The Gotham Election, which was a satire of electioneering and local bribery. The managers of Drury Lane suppressed performance, and it did not debut until 1724 at the Haymarket Theatre.

1716 saw her write The Cruel Gift with Nicholas Rowe, a tragedy, and she followed that with one of her best-known plays, A Bold Stroke for a Wife in 1718. The next year, she fell ill. Her last play, The Artifice, was acted in 1722, and she continued to write poetry after that.

She died on December 1, 1723 and was buried at the actor's church at St. Paul's Church, Covent Garden.

Her comic plays involve extraordinary plots that near the level of farce, and her tragedies and romances usually feature an oppressive (Tory) father who stands in the way of happiness. Bernard Lintot paid her £10 for the copyright to her early plays, while Edmund Curll paid her £21 apiece for three of her later plays. She also received numerous gifts (gold rings, jewelry, gem stones) for dedications. However, she was also a political dramatist who not only allied herself with Whig authors, but who took deliberate pains to strike out at Tories and their causes. For that reason, she was lampooned as, according to Alexander Pope, "the Cook's Wife of Buckingham Court," and by others for having a supposedly mannish appearance. Pope also made her one of the gibbering dunces at the end of Book II of The Dunciad, depicting her as the greatest fan of dull and boring verse alive as she stays awake through a reading of Richard Blackmore's epics longer than anyone except Folly. Nevertheless, her plays would be on the boards for over 150 years after her death.