The venue was the home court of the Los Angeles Lakers of the NBA from October 1960 to December 1967, the Los Angeles Clippers also of the NBA from 1984 to 1999, and the home ice of the Los Angeles Kings of the NHL from October to December 1967 during their inaugural 1967–68 season. It was the home for college basketball for the USC Trojans from 1959 to 2006 and the UCLA Bruins from 1959 to 1965 and again as a temporary home in the 2011–2012 season. It also hosted the Los Angeles Aztecs of the NASL who played one season of indoor soccer there (1980–81), the Los Angeles Blades of the Western Hockey League from 1961 to 1967, the Los Angeles Sharks of the WHA from 1972 to 1974, the Los Angeles Cobras of the AFL in 1988, and the original Los Angeles Stars of the ABA from 1968 to 1970. The arena played host to the top indoor track athletics meet on the West Coast, the annual Los Angeles Invitational track meet (frequently called the "Sunkist Invitational", with title sponsorship by Sunkist Growers, Incorporated), from 1960 until the event's demise in 2004.

The arena hosted the 1960 Democratic National Convention, the 1968 and 1972 NCAA Men's Basketball Final Four, the 1992 NCAA Women's Basketball Final Four, the 1963 NBA All-Star Game, and the boxing competitions during the 1984 Summer Olympics. In addition to hosting the final portion of WrestleMania 2 in 1986, the Los Angeles Memorial Sports Arena also hosted WrestleMania VII in 1991 as well as other WWE events. The arena hosted When Worlds Collide, a 1994 joint card between the Mexican lucha libre promotion Asistencia Asesoría y Administración (AAA) and WCW (which normally called the Great Western Forum home until they, too, moved to Staples Center) that is credited with introducing the lucha style to English-speaking audiences in the U.S. NBC's renewed version of American Gladiators and the 1999–2001 syndicated show Battle Dome were filmed from the arena.

After then-Clippers owner Donald Sterling turned down an agreement to re-locate the franchise permanently to Anaheim's Arrowhead Pond (now Honda Center) in 1996, the Coliseum Commission had discussions to build an on-site replacement for the Sports Arena. Plans included a seating capacity of 18,000 for basketball, 84 luxury suites, and an on-site practice facility for the Clippers. However, as a new Downtown Los Angeles sports and entertainment arena was being planned and eventually built (Staples Center) two miles north along Figueroa Street, the Coliseum Commission scuttled plans for a Sports Arena replacement, and as a result, the Clippers became one of the original tenants at the new downtown arena. There were also similar plans years earlier, in 1989, as Sterling had discussions with then-Los Angeles mayor Tom Bradley and then-Coliseum Commission president (and eventual Bradley mayoral successor) Richard Riordan about a Sports Arena replacement; Sterling threatened to leave the Sports Arena and move elsewhere in the Los Angeles region if plans did not come together.

After the Trojans departed to the new Galen Center in 2006, the arena assumed a lower profile. The arena still continued to hold high school basketball championships, as well as concerts and conventions. The UCLA men's basketball team played a majority of their home games at the Sports Arena during the 2011–12 season while Pauley Pavilion underwent renovation.

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