The infirmary has its origins in a small building on Shaw's Brow which was opened by the 11th Earl of Derby on part of the site which is now occupied by St George's Hall on 25 March 1749.

[1] The second incarnation of the infirmary was designed by John Foster in the Greek Revival style and opened on Brownlow Hill in September 1824.

[2] William Rathbone VI, based on advice from Florence Nightingale, set up the world's first ever district nursing service at this building in 1862.

[2] The foundation stone for a new out-patient building, which incorporated a large hall which could accommodate up to 200 people, was laid by the 17th Earl of Derby on 7 July 1909.

[2] Notable people who have trained and worked at Liverpool Royal Infirmary include: Robert Tressell, author of The Ragged-Trousered Philanthropists, died there in 1911.