The play is named in a document of January 1669, in the Lord Chamberlain's records, as one of twentyone plays of Shakespeare ‘allowed of to’ the King's Company at Theatre Royal, Bridges Street, after the Restoration. The clause ‘formerly acted at the Blackfryers’ clearly implies one or more performances before the closing of the theatres in 1642; but no record of any has been found. Nor is there any evidence that Killigrew's Company ever used its exclusive rights to put the play on the stage. In fact, down to the middle of the nineteenth century all but total neglect seems to have overtaken the play. Only with Phelps's revival in 1849 did the theatrical world begin to take an interest in it—an interest shown by the increasing frequency of revivals to have grown steadily of late.

During the period of eclipse, Shakespeare's tragedy was either superseded by Dryden's play on the same theme, All For Love, or by bad attempts to rewrite Shakespeare's play, or to blend it with Dryden's. In 1677, for example, an Antony and Cleopatra was presented in the Dorset Garden Theatre by the Duke's Company, with Betterton as Antony, Mrs Betterton as Octavia, Mrs Mary Lee as Cleopatra, Mrs Hughes as Charmian, William Smith as Augustus, and Harris as Maecenas. But this was in reality an exceedingly poor version of the story in rhyming verse by Sir Charles Sedley.