The foundation stone for a church to replace the Episcopal Floating Chapel, the "Brazen", was laid on 11 May 1846 by Albert, the Prince Consort. The cost of £9,000 - including £1,250 for the Dock Street site - was met by public subscription, and it was consecrated in 1847. As part of the process, the architect Henry Roberts and several residents of Wellclose Square had issued a householders' certificate of inadequacy of existing churches in the parish of St Mary Matfelon, in which the new church was situated: its patrons, Brasenose College Oxford, gave formal consent, as did the evangelical Rector of Whitechapel from 1837-60, the Rev W.W. Champneys, who was one of the prime movers, and built three other churches in the area, largely maintained by the Church Pastoral Aid Society. St Paul's it did not become a parish church until 1864. The original trustees were Lord Henry Cholmondeley, the Hon. Francis Maude, John Labouchere, Frederick Madan (one of the Elder Brethren of Trinity House) and Charles James Bevan. New trustees were regularly appointed: one of the last, in 1959, was David Sheppard (later Bishop of Liverpool), when he was the Warden of the Mayflower Centre in Canning Town.
The architect was Henry Roberts FSA, Fellow of the Institute of British Architects (1803–76), who was born in Philadelphia but came to work in Britain, in the office of Fowler and Smirke before setting up his own practice in 1830. He had liberal and Evangelical connections. In 1832 he won the competition to design the Fishmongers' Company Hall by the new London Bridge, and the result, in Greek Revival style showing Smirke's influence, was much admired. His practice (with George Gilbert Scott as a pupil) flourished, with houses for the aristocracy in a range of styles - Jacobean, Tudor Gothic and Italianate. His essays in Gothic Revival churches, however, of which St Paul's was an example, did not meet with the approval of the Ecclesiologists. Reviewing the designs in 1846, they judged it extremely poor - a vulgar attempt at First Pointed....the whole is stale and inspid. It was in Early English style, of stock brick, with stone dressings, and a tower and spire at the north-west which was surmounted, not by the customary cross, but by a weather-vane in the form of a ship (now mounted on the south wall of St Paul's School). The interior was plain, with no chancel and a west-end gallery (the organ was in the first stage of the tower.)
In 1971 St Paul's parish was joined to St George-in-the-East but the church remained open for worship until 1990. During that period, the enigmatic Joseph Thomas Davies, known as 'Father Aquinas', was curate-in-charge from 1971-79. Remembered with affection by some for his enthusiasm, he broke all the rules: finances were dodgy, he let vagrants live in various parts of the church, and drove young people around in an untaxed van despite never having taken a driving test. He left to become Rector of Roos in the East Riding, then of four Suffolk villages near Sudbury, from 1989 until his death. Here is Christmas, Easter and Harvest at St Paul's in his time.
In 1989 the St Katharine's Dock area of the parish (south of East Smithfield) was transferred to St Peter Wapping. Various schemes for the church building were considered - including a restaurant, and continued use by other Christian denominations who had been meeting there since it closed for Anglican worship; unfortunately, there was little consultation with the parish. It was on the market for a year, with a £1.5m price tag. The East London Advertiser on 14 September 1990 dubbed it 'the church no-one wants', and the agent commented 'we will push it more aggresively when the property market picks up'. It was used in 1991 for the filming of the first series of the first ever TV show about computer and video games, Gamesmaster, presented by sporting stars of the day, including John Fashanu, Eric Bristow, Jimmy White, Pat Cash, Gary Wilson and Emlyn Hughes. In the event, it was successfully converted into a private nursery in 2002; the parish has had no contact since.