During the 16th century the church was a centre of Reformation preaching, with William Perkins serving as "lecturer" from 1585 until his death in 1602,[2] when he was succeeded by Paul Baynes and Ralph Cudworth.

By 1650 the medieval church building was in a poor state, and it was suggested that the parish be merged with that of Holy Trinity; it was however rebuilt largely at the expense of Christopher Rose (twice Mayor of Cambridge, in 1637 and 1654).

Thomas Tenison, Archbishop of Canterbury from 1694, was curate of St Andrew's from 1662, where he set an example by his devoted attention to sufferers of the plague.

[5] It was rebuilt with a nave of five bays with side aisles and a west tower of four stages; the south porch and vestries were added later in the 19th century.

It does however retain elements of the earlier structure including early 12th-century double capitals in the heating chamber and some wall memorials, notably that of Captain James Cook and his family.

[13] The parish has passed resolutions to reject the ordination and/or leadership of women, and it receives alternative episcopal oversight from the Bishop of Ebbsfleet (currently Rob Munro).