Destroyed in the Great Fire, St Mary Somerset was one of the 51 churches rebuilt by the office of Sir Christopher Wren.

Pre-Fire London had 14 churches named after the Virgin Mary, six of which were rebuilt after the Fire. The derivation of ’Somerset’ is uncertain. It has been linked to Ralph de Somery, who is mentioned in records at the same time. It is also linked to Summer’s Hithe, a small haven on the Thames, the banks of which would have been closer in medieval times. The church was first mentioned in a deed during the reign of Richard I.

According to John Stow, in 1370, the Brabant weaver community was ordered by the Mayor to meet in the churchyard of St Mary Somerset for the purpose of hiring serving men, following disputes with the Flemish weavers. The latter were ordered to meet a safe distance away in the churchyard of St Laurence Pountney.

After the Fire, the parish was combined with that of St Mary Mounthaw, which was not rebuilt. Building of the new church began in 1686 (one of the last 5 of the 51 to commence) and stopped in 1688 owing to the financial uncertainty associated with the Glorious Revolution. Rebuilding recommenced the next year and the church was finished in 1694, at a cost of £6579.

The parish was very poor, and it was one of only two churches (the other being St. Andrew-by-the-Wardrobe) for which Wren provided funds for the furnishings from the Coal Tax. The rebuilt church was smaller than its predecessor, as a strip of land was taken by the City to widen what was then Thames Street.

Bishop Gilbert Ironside, Chancellor of Oxford University, who defied James II in upholding the rights of Fellows, was buried here in 1701. His remains, and black marble tombstone, were removed to Hereford Cathedral in 1867.

The second half of the 19th century saw a movement of population from the City of London to suburbs in Middlesex, Kent, Essex and Surrey. This left many of the city churches with tiny congregations, while many of the newly built suburbs had no churches. The Union of Benefices Act 1860 was passed by Parliament, permitting the demolition of City churches and the sale of land to build churches in the suburbs. The last service at St Mary Somerset was held on 1 February 1867, with about 70 people attending. The parish was then combined with that of St Nicholas Cole Abbey, and the church demolished in 1871.

At the instigation of the architect, Ewan Christian, the church tower was preserved. The proceeds of the sale were used to build St Mary Hoxton, which also received the church furnishings and the bell.