Walton was born at Stafford. His father, an innkeeper, died when Izaak was very young. His mother then married another innkeeper.

He settled in London where he began trading as an ironmonger. In 1614 he had a shop in Fleet Street, and around this time he became friendly with Dr John Donne, then vicar of the parish church.

Walton's first wife was Rachel Floud (married December 1626), a great-great-niece of Archbishop Cranmer. She died in 1640. Not long after this, he married Anne Ken (Kenna of The Angler's Wish) stepsister of Thomas Ken, afterwards bishop of Bath and Wells.

As a Royalist, Walton felt unsafe under Cromwell’s rule and left London for Stafford, where he had bought some land; but by 1650 he was again living in Clerkenwell. The first edition of The Compleat Angler was published in 1653. Anne died in 1662, and was buried in Worcester Cathedral. Walton then moved to Winchester, where he died December 15,1683. He was buried in the Cathedral.