The presence of Presbyterianism in Cambridge had dwindled through the eighteenth century. In the nineteenth century, many Scots and Irish Presbyterians began to move to the area to pursue careers in business, the professions and academia. This gave Presbyterianism in Cambridge a fresh impetus.
Until 1871, members of Cambridge colleges were required to attend worship in the Anglican college chapels. As this regulation was relaxed, more and more Presbyterians, mostly Scots, entered the University, and the demand for a congregation of the Presbyterian church in Cambridge grew. In 1879, the first congregation of the Presbyterian church in Cambridge met in the Guildhall. Work on the present church building began in 1890, and the new church was opened on 7 May 1891. In November 1893 the Presbytery approved the name of St Columba, ‘the presbyter-apostle of Iona’.

Westminster College, a theological college of the Presbyterian Church of England came to Cambridge in 1899. This had a great influence over the life of St Columba’s, with many prominent theologians teaching at the college also becoming deeply involved in the life and preaching of the church. To this day, St Columba’s continues to benefit from the intellectual and spiritual work of those who teach at Westminster.

In 1972, the Presbyterian Church of England united with the Congregational Church in England and Wales to form the United Reformed Church, of which St Columba’s is now a part, with further unions in 1981 with the Churches of Christ and in 2000 with the Congregational Church of Scotland.