The present domed building was erected to the designs of Sir Christopher Wren following the destruction of its medieval predecessor in the Great Fire of London in 1666.

The original church is thought to have been built directly over the remains of a Roman Mithraic Temple following a common Christian practice of hallowing former heathen sites of worship.

In 1429 Robert Chichele, acting as executor of the will of the former Lord Mayor, William Standon, had bought a piece of land close to the Stocks Market (on the site of the later Mansion House) and presented it to the parish.

[11] The walls, tower,[12] and internal columns [3] are made of stone, but the dome is of timber[12] and plaster with an external covering of copper[13] The 63 feet (19 m) high dome is based on Wren's original design for St Paul's, and is centred over a square of twelve columns[14] of the Corinthian order.

The contemporary carved furnishings of the church, including the altarpiece and Royal Arms, the pulpit and font cover, are attributed to the carpenters Thomas Creecher and Stephen Colledge, and the carvers William Newman and Jonathan Maine.

In 1776 the central window in the east wall was bricked up to allow for the installation of Devout Men Taking Away the Body of St Stephen, a painting by Benjamin West, which the rector, Thomas Wilson, had commissioned for the church.

In 1987, as part of a major programme of repairs and reordering,[17] a massive white polished stone altar commissioned from the sculptor Henry Moore by churchwarden Peter Palumbo was installed in the centre of the church.

[22] Benjamin West's Devout men taking away the body of St Stephen, previously hung on the north interior wall, was put into storage following the reordering.

[26] At the time of his retirement in 2003, at the age of 92, Dr Chad Varah was the oldest serving incumbent in the Church of England.