The main site is located just behind St Marylebone Parish Church, with the Sixth Form Centre based in another building nearby at Blandford Street.

In 1808, with the support of local philanthropist and social reformer Sir Thomas Bernard, the school moved to 82 Marylebone High Street, which is now a boutique store.

Subsequently, to make room for growing numbers, it moved to a site on Paddington Street, which is identifiable today as a Mission Church.

Then in 1858 the 5th Duke of Portland bought a plot of ground near the top of Marylebone High Street and covenanted the site to be used for a girls' school in perpetuity.

Popular videos shot at this location include "Little Miss High and Mighty" and "Hard Knock Life".

The houses are named after these significant people as they have had some kind of connection with the school (e.g. Thomas Hardwick designed the St Marylebone Church).

Dickens's house has been renamed 'Dove' after Evelyn Dove who studied at the Royal Academy of Music which is located close to the school.

The houses have the following colours: blue (Barret), yellow (Dove), red (Hardwick), green (Wesley), purple (Nightingale) and orange (Ada).

Mrs Phillips, who is a National Leader of Education, was appointed executive head teacher of the St Marylebone Academies Trust in 2010 and was chair of the Westminster Secondary Heads Forum, representing secondary headteachers on the 14-19 Executive Board.

[citation needed] St Marylebone is one of the most oversubscribed schools in London; in 2013, almost 7 students applied for each of the places available in Year 7.