Flatman was the son of a clerk in Chancery and was born in Aldersgate Street and educated at Winchester College.
He was a staunch Royalist and one of his poems was to celebrate the return of Charles II in 1660 after the collapse of the Cromwellian Commonwealth.
Among his earliest verses are lines prefixed to Graphice (1658) by Sir William Sanderson, a work containing a description of the art of miniature painting, based on Edward Norgate's writings.
Flatman divided his career between writing poetry (in which his earnest religious temperament is revealed) and painting portraits in miniature.
Alexander Chalmers attributes the satirical work Don Juan Lamberto, or a Comical History of the late Times to Flatman in his entry in the General Biographical Dictionary of 1812–1817.