Cut loose by Elektra, they changed their name again, to Blue Öyster Cult, and signed to Columbia Records in late 1971, by which time Winters had been replaced by Albert Bouchard's brother Joe. Blue Öyster Cult, their debut album, was released in January 1972 and made the lower reaches of the charts. Columbia sent a promotional EP, Live Bootleg, to radio stations in October, and followed with BÖC's second album, Tyranny & Mutation, in February 1973. Their third album, Secret Treaties, was released in April 1974 and became their first to break into the Top 100 bestsellers. (It eventually went gold.) BÖC released a live double album, On Your Feet or on Your Knees, in February 1975.

In May 1976 came their fourth studio album, Agents of Fortune, including the Top 40 (Top Ten on some charts) hit single "(Don't Fear) The Reaper" (featured in the classic John Carpenter horror film Halloween), which became their first gold and then platinum album. (On Your Feet went gold shortly after.) BÖC's sixth overall album, Spectres, was released in October 1977 and went gold in January 1978. In September 1978 came a second live album, Some Enchanted Evening, which eventually would become BÖC's second million-seller, followed by the studio album Mirrors in June 1979. A year later, BÖC released its ninth album, Cultosaurus Erectus, with the gold Fire of Unknown Origin, containing the Top 40 hit "Burnin' for You," following in June 1981.

In the summer of 1981, drummer Albert Bouchard was replaced by the band's tour manager and lighting designer, Rick Downey. BÖC's third live album, Extraterrestrial Live, was released in April 1982, followed by the studio album The Revolution by Night in October 1983. Downey left in 1984 and was replaced in 1985 by Jimmy Wilcox. The same year, Lanier left and was replaced by Tommy Zvonchek. BÖC released its 13th album, Club Ninja, in January 1986. Bassist Joe Bouchard left in 1986 and was replaced by Jon Rogers. In 1987, Lanier returned to the group, and Ron Riddle replaced Wilcox on drums. BÖC's 14th album, the concept recording Imaginos, became their final new album on Columbia Records in July 1988. BÖC scored the movie Bad Channels in 1992, by which time Chuck Burgi had replaced Ron Riddle on drums. In 1994, Blue Öyster Cult released Cult Classic, an album of re-recorded favorites, in connection with the use of their music in the TV miniseries of horror novelist Stephen King's The Stand. Numerous lineup changes ensued throughout the '90s (as the band kept on touring the world), and in 1995, were the subject of a double disc anthology, Workshop of the Telescopes.

By the late '90s, BÖC had signed with the CMC label, resulting in their first album of all-new studio material in ten years, 1998's Heaven Forbid, and three years later The Curse of the Hidden Mirror. The group's music reached a whole new generation of hard rock fans when Metallica covered the BÖC classic "Astronomy" for their best-selling Garage Inc. album in 1998, as a few other best-of collections surfaced around the same time -- Super Hits and Don't Fear the Reaper: The Best Of. In 2001, Columbia/Legacy reissued BÖC's first four releases with a newly remastered sound and added bonus tracks.