[1] The street was gradually developed by a senior branch of the Cavendish-Bentinck family, the Dukes of Portland, who owned most of the eastern half of Marylebone in the 18th and 19th centuries.

The Berners family owned land to the east; they developed Wells Street and Rathbone Place in the mid-18th century.

The layout, combined with its width and the concentration of shops along its length, means it has for a long time been a local centre and thoroughfare, connecting the residential areas around Regent's Park with the West End.

This had an effect during its redevelopment in the late-19th/early-20th centuries when rebuilding was dictated by the expiration of individual 99-year leases, and is evident in the buildings in existence today.

Double Negative (VFX), a British full-service motion picture company, is located on the Great Portland Street.

Other manufacturers, including the big names of Vauxhall, Jaguar, Austin, Auto-Union DKW, and the DORT Motor Company were also represented on the street in the first decades of the last century.

[19] The German composers Felix Mendelssohn (1809–1847) and Carl Maria von Weber (1786–1826) both lived and worked on Great Portland Street.

[20] №103 is cited as one of "London's 50 Outstanding Classical Music Landmarks" because Felix Mendelssohn lodged there during the premiere of Fingal's Cave.

[21] Other notables living on the street include James Boswell, 9th Laird of Auchinleck, biographer at №122, Leigh Hunt the essayist and poet at №98, and the artist David Wilkie at №117 (1808–09).

[24] Pagani's restaurant, with its art nouveau frontage by Beresford Pite, was a favourite gathering place for many artists and musicians.

[30] Great Portland Street still hints at its past when it was a major centre for London's women's clothing industry.

Over time, these grew into larger showrooms which represented the English textile industry to many West End stores.

Its proximity to buying officers working for the big stores on Oxford Street gave businesses in the area a competitive edge.

The sector's local presence declined in the late 1970-80s with the disappearance of both the UK's independent retailer and the British textile industry.

Major names of the garment industry associated with the street include Shubette of London, Coppernob, Alfred Young, Hildebrand and French Connection.

[37] The present station building, designed by Charles Clark, is of 1930 date and is constructed from cream faience tile with a slate mansard roof.