The church, which dated back to medieval times stood on the south side of Thames Street, at the corner of Botolph Lane.
During the 15th century the church was extended to the south over an undercroft. On the south side of this extension, at the south-east corner of the enlarged church, was a small stone-built vestry, which also had a cellar beneath. The parish rented out these cellars, usually to the same tenant. Archaeological excavations beneath part of the Billingsgate Lorry Park in 1982 uncovered the remains of the vault beneath the aisle of the church, and what may have been those of the one beneath the vestry.
A piece of land, formerly used as a passageway was given to the parish by the City corporation for use as an additional churchyard. Having been enclosed within a brick wall, it was consecrated in 1617. In 1620 the church was "repaired and beautified" at a cost of more than £600.
St Botolph Billingsgate was destroyed in the Great Fire of London in 1666 and not rebuilt. Instead the parish was united to that of St George Botolph Lane. The site of the church and its adjoining churchyard continued to be used for burials, although a house was built on part of the site of the nave and rented out by the parish, and in around 1677 a shop was built above a newly constructed burial vault in the churchyard and leased out for the benefit of the poor at a rent of £4 a year; a second vault was built, and a shop built over it in 1693. In the same year the site of the chancel was sold and the land used to widen the lane between Thames Street and Botolph Wharf.
The upper churchyard was also retained as a burial ground for the united parishes. It survives as a privately owned garden at the corner of Monument Street and Botolph Lane, under the name of "One Tree Park".