It played a formative role in the emergence of Britain's skiffle and rock and roll music culture in the late 1950s, and several major stars including Tommy Steele and Cliff Richard were first discovered performing there.

The stage area can very briefly be seen in Rank Studio's 1959 episode "Coffee Bar", from their Look at Life, available on Network DVD, in a clip featuring future Shadows drummer Brian Bennett.

[3][6] Several recording stars were discovered at, or performed at, the 2i's coffee bar, including Rory Blackwell, Tommy Steele, The Vipers Skiffle Group, Cliff Richard, Hank Marvin, Bruce Welch, Brian Bennett, Tony Meehan, Jet Harris, Brian 'Licorice' Locking, Vince Eager, Terry Dene, Wee Willie Harris, Adam Faith, Carlo Little, Joe Brown, Clem Cattini (The Tornados), Eden Kane, Screaming Lord Sutch, Tony Sheridan, Keith Kelly,[7] Russ Sainty, Lance Fortune, Albert Lee, Johnny Kidd, Paul Gadd (later to be known as Paul Raven and then Gary Glitter), Ritchie Blackmore, Alex Wharton, Mickie Most (as the Most Brothers),[8] Big Jim Sullivan, Joe Moretti, Vince Taylor, Duffy Power, Johnny Gentle, Michael Cox, Kris Kristofferson, Derry and the Seniors and Georgie Fame.

[6] According to Chas McDevitt, Bart was responsible for painting the cellar, decorating it with a "black ceiling, large, stylised eyes on the walls, and cubist shapes behind the small stage platform".

[11] The 2i's rapid success led to the opening of a second branch at 44 Gerrard Street, in what had been a folk and skiffle club run by John Hasted, before the end of 1956, although it soon closed due to intimidation by organised crime.

The 2i's was the inspiration for the establishment of the Casbah Coffee Club in Liverpool by Mona Best in the cellar of her family home, which played an important role in the early development of the Beatles.

During their time in Hamburg the band worked with Tony Sheridan, who had performed at the 2i's, and later recruited another 2i's veteran, Jimmie Nicol, to fill in for Ringo Starr on an Australian tour.

[6] On 18 September 2006, a green plaque was unveiled at the site of the 2i's Coffee Bar to commemorate its existence, and to celebrate 50 years of British rock and roll.

[6] Marc Bolan later reported that as a youth he had regularly attended the bar (in close proximity to his mother's Berwick Street market stall) and had once witnessed an unsuccessful audition by Richard at the venue.