It hosts a year-round exhibitions programme as well as events, performances and activities.

The three-storey gallery was opened in February 2017 as part of that year's Hull UK City of Culture event, with exhibitions by the COUM Transmissions collective and Sarah Lucas.

[1] Humber Street Gallery has since housed exhibitions from artists such as Bloomberg New Contemporaries 2022, Hetain Patel, Oliver Ressler and more.

The gallery's café includes the local "Dead Bod" graffiti,[2] relocated from its original site on a corrugated iron shed on Riverside Wharf.

[3] The artwork is a human-sized depiction of a dead bird, supposedly painted by Captain Len ‘Pongo’ Rood and Chief Engineer Gordon Mason in the 1960s, and was a prominent feature on the city's docks.