Francis was born in Romford, Essex, (now London Borough of Havering), and baptised there on 8 May 1592. He traced his ancestry to a family settled in England before the Norman Conquest with a long history in royal service. His great-grandfather, George Quarles, was Auditor to Henry VIII, and his father, James Quarles, held several places under Elizabeth I and James I, for which he was rewarded with an estate called Stewards in Romford. His mother, Joan Dalton, was the daughter and heiress of Eldred Dalton of Mores Place, Hadham. There were eight children in the family; the eldest, Sir Robert Quarles, was knighted by James I in 1608, and another, John Quarles, also became a poet.

Francis was entered at Christ's College, Cambridge, in 1608, and subsequently at Lincoln's Inn. He was made cupbearer to the Princess Elizabeth, in 1613, remaining abroad for some years; and before 1629 he was appointed secretary to Ussher, the primate of Ireland.

About 1633 he returned to England, and spent the next two years in the preparation of his Emblems. In 1639 he was made city chronologer, a post in which Ben Jonson and Thomas Middleton had preceded him. At the outbreak of the Civil War he took the Royalist side, drawing up three pamphlets in 1644 in support of the king's cause. It is said that his house was searched and his papers destroyed by the Parliamentarians in consequence of these publications.

Quarles married Ursula Woodgate in 1618, by whom he had eighteen children. His son, John Quarles (1624—1665), was exiled to Flanders for his Royalist sympathies and was the author of Fons Lachrymarum (1648) and other poems. Quarles descendants, Charles Henry Langston and John Mercer Langston were American abolitionist whom pressed for greater freedom and suffrages among the African Americans in the 19th century.

The work by which Quarles is best known, the Emblems, was originally published in 1635, with grotesque illustrations engraved by William Marshall and others. The forty-five prints in the last three books are borrowed from the designs by Boetius à Bolswert for the Pia Desideria (Antwerp, 1624) of Herman Hugo. Each "emblem" consists of a paraphrase from a passage of Scripture, expressed in ornate and metaphorical language, followed by passages from the Christian Fathers, and concluding with an epigram of four lines.

The Emblems was immensely popular with the common people, but the critics of the 17th and 18th centuries had no mercy on Quarles. Sir John Suckling in his Sessions of the Poets disrespectfully alluded to him as he "that makes God speak so big in's poetry." Pope in the Dunciad spoke of the Emblems, "Where the pictures for the page atone And Quarles is saved by beauties not his own."

The works of Quarles include:

• A Feast for Wormes. Set forth in a Poeme of the History of Jonah (1620), which contains other scriptural paraphrases, besides the one that furnishes the title; Hadassa; or the History of Queene Ester (1621)
• Job Militant, with Meditations Divine and Moral (1624)
• Sions Elegies, wept by Jeremie the Prophet (1624)
• Sions Sonets sung by Solomon the King (1624), a paraphrase of the Canticles
• The Historic of Samson (1631)
• Alphabet of Elegies upon ... Dr Aylmer (1625)
• Argalus and Parthenia (1629), the subject of which is borrowed from Sir Philip Sidney's Arcadia
• four books of Divine Fancies digested into Epigrams, Meditations and Observations (1632)
• a reissue of his scriptural paraphrases and the Alphabet of Elegies as Divine Poems (1633)
• Hieroglyphikes of the Life of Man (1638)
• Memorials Upon the Death of Sir Robert Quarles, Knight (1639), in honor of his brother
• Enchyridion, containing Institutions Divine and Moral (1640—41), a collection of four "centuries" of miscellaneous aphorisms
• Observations concerning Princes and States upon Peace and Warre (1642)
• Boanerges and Barnabas--Wine and Oyle for ... afflicted Soules (1644—46), collection of miscellaneous reflections
• three violent Royalist tracts (1644), The Loyal Convert, The Whipper Whipt, and The New Distemper, reissued in one volume in 1645 with the title of The Profest Royalist
• his quarrel with the Times, and some elegies
• Solomon's Recantation ... (1645), which contains a memoir by his widow
• The Shepheards' Oracles (1646)
• a second part of Boanerges and Barnabas (1646)
• a broadside entitled A Direfull Anathema against Peace-haters (1647)
• an interlude, The Virgin Widow (1649).

An edition of the Emblems (Edinburgh, 1857) was embellished with new illustrations by CH Bennett and WA Rogers These are reproduced in the complete edition (1874) of Quarles included in the "Chertsey Worthies Library" by Dr AB Grosart, who provides an introductory memoir and an appreciation of Quarles's value as a poet.