Marlborough is a market town sitting on the confluence of the the river Kennet and its tributary, the river Og; it is about 10 miles S of Swindon. The church lies to the centre of the town and was possibly built on a site formerly occupied by a Saxon church. The current W door and the former W respond of the N nave arcade date from the 12thc. There is some evidence of the development of the church during the later Middle Ages, but the major event in the church's history was the fire of 1653 that destroyed most of the church and much of the town. The nave was rebuilt with a tall, single arcade, leaving the NW respond as a redundant reminder of the earlier church.

The Domesday Book records that in 1086 William of Beaufour held a hide of land along with a church in Marlborough; it was worth £1.5. In 1091 Bishop Osmund endowed the chapter of Old Sarum with the churches in Marlborough and St Mary’s was specifically mentioned in 1223. However, Pevsner and the DCMS listing description mention that the church was founded in 1160, though no source is cited. The surviving Romanesque fabric would be consistent with this date.

Galleries were added to the nave in 1707 and the chancel was rebuilt in 1873-4 to designs by George Edmund Street. The church was restored again in 1955-7.