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The first parish church of Paddington stood on Paddington Green and was probably dedicated to Saint Katherine. This was demolished in 1678 and replaced by a church dedicated to Saint James. This in turn was demolished and replaced by Saint Mary's, which was constructed between 1788 and 1791. It became the parish church. In 1845 it was superseded by the newly constructed and larger church of Saint James, Sussex Gardens (P87/JS). Most of the older parish records were transferred in 1845 from Saint Mary's to Saint James.
Saint Mary's became a district chapelry. Actress Sarah Siddons (born 1755) was buried here in June 1831. Other notable graves are those of B R Haydon, the painter of gigantic historical canvases who committed suicide (1846), artist William Collins RA (1847), Sarah Disraeli, the statesman's favourite sister; and Harriet, the unhappy first wife of poet Percy Bysshe Shelley, who drowned herself in the Serpentine after he had deserted her (1816).