He wrote a number of farces, amusing dramatic pieces and librettos for pasticcio operas, many of which had great success.

[1] After showing a talent for drawing he studied art at an academy in Dublin, but grew increasingly more interested in the theatre.

[3] The marriage ended badly when O'Keeffe discovered that she was having an affair with the Scottish actor George Graham.

The following year he wrote Tony Lumpkin in Town, a sequel to Oliver Goldsmith's She Stoops to Conquer, and sent it to the manager of the Haymarket Theatre.

O'Keeffe also wrote The Son-in-Law, Agreeable Surprise (which includes the lyrical poem Amo, Amas), and The Castle of Andalusia.

O'Keeffe contributed many Irish folksongs to the musical scores by Samuel Arnold and Shield such as I am a Friar of Orders Grey and The Thorn are still popular.

In 1826, O'Keeffe wrote his memoirs, which covered his life experiences and various interactions with the leading artistic figures of his day.

[11] In the 19th century, the essayist William Hazlitt described O'Keeffe as the "English Molière", observing "in light, careless laughter and pleasant exaggeration of the humorous, we have no equal to him".