It was opened January 11, 1964 at the site of an old bank building that had been remodeled into a short-lived club called the Party, by a former Chicago policeman, Elmer Valentine. Valentine's partners were lawyer Theodore F. Flier, former press agent Shelly Davis, and Phil Tanzini.
Though the club was billed as a discothèque, meaning only recordings with no bands, the Whisky A Go-Go opened with a live band led by Johnny Rivers and a short skirted DJ spinning records between sets from a suspended cage at the right of the stage. When the girl DJ danced during Rivers' set, the audience thought it was part of the act and the concept of Go-Go dancers in cages was born. Rivers rode the Whisky-born "go-go" craze to national fame with records recorded partly "live at the Whisky." The Miracles recorded the song Going to a Go-Go in 1966, which was covered in 1982 by The Rolling Stones, and Whisky A Go-Go franchises sprang up all over the country.
In 1966, the Whisky was one of the centers of the Sunset Strip police riots. The club was harassed repeatedly by the City of Los Angeles, which once ordered that the name be changed, claiming "whisky" was a bad influence. It was the "Whisk?" for a while.
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.