He was named after his grandfather, John Isham of Lamport Hall (1525-1595), who had made enough of a fortune as a London wool merchant to acquire an extensive estate near Lamport, Northamptonshire where in 1568 he built a manor house.
In 1611 he was appointed to High Sheriff of Northamptonshire, a post that his grandfather, the elder John Isham, had held 30 years before.
Wealthy and successful, Isham became a member of the aristocracy when Charles I on 30 May 1627 created him the first hereditary Baronet of Lamport.
The title of baronet subsequently passed down to his only son Justinian Isham.
His daughter Elizabeth Isham is known for her diary, which is one of the earliest known examples of an autobiography written by a woman.