Originally intended as the private chapel of the adjacent St Mary's Hall school, it was partly built in 1838 at the request of Frederick Hervey, 1st Marquess of Bristol; but arguments over whether or not it should also be open to the public delayed its completion for more than 10 years.

Brighton's rapid growth in the early decades of the 19th century resulted in residential development filling in the gap on the cliffs between Thomas Read Kemp's high-class Kemp Town estate and the longer-established area around the Royal Pavilion and Old Steine, the centre of high society activity in the late 18th century.

Soon after buying the land, he gave a portion to Reverend Henry Venn Elliott to allow him to build St Mary's Hall School.

[3] In 1837, Reverend Elliott began to plan for an Anglican church to serve the area, and the Marquess gave more land next to the school to allow one to be built there.

[5] Construction was allowed to continue in 1848, after agreement was reached that the church could be used for public worship, and the Bishop of Chichester Ashurst Turner Gilbert conducted a consecration ceremony on 21 September 1849.

[5][6] The identity of the architect was not recorded, but sources suggest either George Cheesman Jr.—whose Christ Church in Montpelier Road, Brighton was very similar—or Thomas Cooper.

Nikolaus Pevsner wrote of its "terrible stone facing",[16] while Harry Stuart Goodhart-Rendel considered both St Mark's and the very similar Christ Church (now demolished) to have "deplorable architecture [...] combining the smugness of the chapel [with] the peculiarity of the Gothic".

[17] The building does not reflect ecclesiastical architectural norms of the mid-19th century, partly because its construction started several years earlier and also because Reverend Elliott and the Marquess of Bristol held traditionalist, old-fashioned views.

[7] As originally designed, the nave and its adjacent aisles consisted of one open-plan area demarcated by narrow cast iron columns and piers.

[7] The galleries, altered and mostly removed during the 1891–1892 work, originally ran round three sides of the interior and were held up by fluted columns.

[6][19] The school made some internal alterations to the church to allow part of it to be used as an arts centre and concert hall, but its main function is still religious.