Quarles matriculated at Exeter College, Oxford, on 9 February 1643, but does not seem to have taken a degree.

During the English Civil War, Quarles joined the Royalist cause and served as a soldier at the garrison at Oxford, England.

While in banishment in Flanders he wrote the poems contained in his first published volume, Fons Lachrymarum.

The published works of Quarles are: There is nothing in the book to show that this last item, a translation entirely in the manner of Quarles, is a posthumous publication, but the date of his death given above is confirmed by William Winstanley, who was apparently acquainted with at least one member of his family.

Quarles also wrote a prose preface to John Hall's Emblems, 1648, and contributed verses to Thomas Fuller's Abel Redevivus (1651).