Born in Seville, where he was baptised Juan Bartolomé Esteban on January 1618. Murillo was his mother's name, Esteban his father's. He studied in Seville c. 1633-8 with Juan del Castillo. In 1645 he married Beatriz Cabrera (d. 1663) by whom he had nine children.
His first decorative cycle, eleven canvases for the monastery of S. Francisco, Seville, was completed in 1646, and his first works for Seville Cathedral were delivered in 1655. Between April and December 1658 he visited Madrid, where his townsmen Velázquez, Zurbarán and Cano were then working. In 1660 he was a co-founder of the Seville Academy, but his interest in it was not sustained. In 1662 he was made a Tertiary of the Franciscan Order. His greatest activity occurred in the decade after 1662 when he completed commissions for the Church of S. Maria la Blanca, the Capuchin Church (see The Virgin and Child with Saints), the Hospital de la Caridad and the Cathedral, all in Seville. He died in Seville on 3 April 1682 after a fall while painting the large Marriage of S. Catherine for the high altar of the Capuchin Church in Cádiz.