There was a priest at Shepperton in 1086 and a church is referred to in 1157. The church continued to serve the whole parish until 1949 when the northern part was transferred to Littleton ecclesiastical parish.

Westminster Abbey was said to hold Shepperton church in 1157, but it did not appropriate the church properly to its own use except for the tithes of its own demesne at Halliford. These, or most of them, had been appropriated by 1291, but there were subsequently a number of disputes about them between the abbey and the rector. The rector acknowledged the abbey's right to them in 1305 and in 1410 he was awarded a pension of 16s. 8d. instead of them. This was not in fact paid then or for many years, but in 1758 the lessee of Halliford manor was ordered to pay eighteen years' arrears of it.

In 1843 138 acres of the parish were exempt from tithes because of this appropriation. The church itself, excluding the appropriated tithes, was valued at £14 13s. 4d. in 1291. In 1535 the living was valued at £26. By the early 18th century it had risen to £230 and by 1835 to £500 net. In 1843 the tithes were commuted for about £550. In 1955-6 the endowment provided £213 net out of an income of £607 net. In 1086 the priest held 15 acres of land, and the glebe was estimated at 19 acres in 1650. It covered 12 acres in 1843, but only a few acres of this still belonged to the living in 1957. The rectory house is described elsewhere: part of it was divided into flats in 1956.

The advowson of the church presumably belonged to Westminster Abbey in 1157 and passed afterwards to their undertenants of the manor. In 1251 the Master of the Hospital of Domus Dei at Dover quitclaimed the advowson to Robert Beauchamp the younger, probably the lord of the manor. The lords continued to present, except on occasions which probably represent grants of single turns, until 1660. From 1683 presentations were made by different persons on each occasion, including the lord of the manor in 1704 and a former lord in 1753.

After 1750 most of the rectors seem to have been presented by relatives or to have presented themselves. By 1913 Mrs. Mary Pickering (d. 1930) held the patronage. She left it to the Society for
the Propagation of the Gospel, the Representative Church Council of the Episcopal Church in Scotland, and the Poor Clergy Relief Corporation. It was transferred to the Bishop of London in 1942.

The light of the Holy Cross is the only one in the church to which there are specific references in the Middle Ages, but in 1547 an unnamed light had an endowment of an acre of land. One medieval rector (1305-30) is known to have been a pluralist and probably did not reside. William Grocyn, the scholar, was rector from 1504 to 1513, but he held other preferments and did not reside at Shepperton. Nicholas Robinson, rector 1561-74, held Shepperton in commendam after becoming Bishop of Bangor in 1566.

He made a twelve-year lease of the rectory estate about 1562. Lewis Hughes, an outspoken royalist, was deprived in 1642. He was said to have taken services after his deprivation and to have forbidden parishioners to pay tithes to John Doddridge in 1647. Doddridge who was the third minister since Hughes had been deprived, was in turn ejected in 1660 but for some time refused to give up the rectory. His successor, Richard Peacock, was a royalist and had been a chaplain to the army in the Civil War. Matthew Kirby was deprived in 1707 for failing to take the oath of allegiance.

His successor Lewis Atterbury, brother of the Bishop of Rochester, was chaplain to Queen Anne, who presented him to Shepperton: he probably did not live there though he took enough interest in the church to contribute largely to building a new tower. In the early 18th century there were two Sunday services and about the end of the century there were seven communion services a year. In 1790 there were some 40 communicants, on Easter Sunday 1821 there were 37, and three years later there were 50. William Russell, rector 1817-70, lived in Shepperton and took an active part in local affairs.

It was afterwards said that when he started his work among them the parishioners 'by all accounts had for some time been living in great darkness and were morally and religiously much in need of a Christian Minister'. In 1870 a chapel of ease called St. John's was opened in Watersplash Road. It and the surrounding district were transferred to Littleton parish in 1949 and the church was closed about 1953. In 1959 there were 351 names on the electoral roll of St. Nicholas. The main Sunday service was then 11 o'clock matins except when it was replaced once a month and on great festivals by sung eucharist.