More rock and roll history has taken place in this one building than in most of the cities in the United States combined. Go-go girls, miniskirted dancers in cages, was started here in the early 60's and started a craze and a national chain of "Whisky-A-Go-Go" s.

The rock and roll scene in Los Angeles was born when the Whisky started operation. From rock to punk to heavy metal, the club stood at the forefront of many musical trends.

The Whisky played an important role in many musical careers, especially for bands based in Southern California. The Byrds were regulars and The Doors were the house band for a while. Frank Zappa's Mothers of Invention got their record contract based on a performance at the Whisky. Jimi Hendrix came by to jam when Sam & Dave headlined. Otis Redding recorded his album Live at the Whisky there in 1966. The Turtles performed there when their newest (and biggest-selling) single "Happy Together" was becoming a hit, only to lose their new bassist, Chip Douglas (who had arranged the song), to the Monkees; guitarist Michael Nesmith invited him to become their producer. (He returned to the Turtles a year later, to produce them.)

Many British performers made their first headlining performances in the area at the Whisky, including The Kinks, The Who, Cream, Led Zeppelin, and Roxy Music. The Whisky was a focus of the emerging New Wave and punk rock movements in the late 1970s, and frequently presented local acts as diverse as The Germs, The Runaways, X and Van Halen while playing host to early performances by the Ramones,The Dictators, Blondie, Talking Heads, Elvis Costello, XTC, The Jam, Japanese doo-wop musical group Rats & Star, including a famous sex offender Masashi Tashiro, among others.

The Whisky fell on hard times once the first flush of punk rock lost steam, and closed its doors in 1982. They reopened in 1986 as a "four-wall", a venue that could be rented by promoters and bands.