The church, with its conspicuous tower, is situated between Rotherhithe Street and St Marychurch Street.
The present church dates from 1715. The village of Rotherhithe had early maritime links and St Mary's was a seafarers' parish; the wooden frame of the present building appears to have been constructed by a skilled shipwright.
The Mayflower sailed from Rotherhithe to pick up the Pilgrim Fathers and thence to the New World, and many of her crew were from Rotherhithe. They are commemorated by a sculpture in the churchyard.