Drafted eighth overall in the 1986 NFL Draft out of Oklahoma State—where he was a two-time consensus All-American—Leslie O'Neal immediately delivered one of the most explosive introductory stretches by a pass rusher in league history. Stepping into the starting lineup for the San Diego Chargers, he terrorized opposing backfields right out of the gate, compiling an astonishing 12.5 sacks in his first 13 professional games to capture AP Defensive Rookie of the Year honors and earn a spot on the PFWA All-Rookie Team.

However, what promised to be a legendary rookie campaign turned tragic in Week 14 against St. Louis, when O'Neal suffered a devastating knee injury that tore multiple ligaments. The severe damage forced him into a grueling rehabilitation process that stripped away his entire 1987 season and kept him sidelined for the first half of 1988.

After returning full-time, O'Neal shifted to outside linebacker and rewarded San Diego's patience in 1989 with an explosive full-season comeback. With his trademark burst off the edge, he racked up 12.5 sacks and earned his first Pro Bowl selection, instantly reaffirming his place among the game's premier defenders.

Moving back to his natural defensive end spot in 1992, O'Neal kicked off a dominant four-year run of Pro Bowl selections from 1992 through 1995. He reached double-digit sacks in five distinct seasons for the Bolts, headlined by a career-high 17.0 sacks in 1992 that co-led the entire NFL. In 1994, he anchored a fierce defensive unit that carried San Diego to an AFC Championship and the franchise's first Super Bowl appearance (Super Bowl XXIX).

Following nine active seasons in Southern California, O'Neal departed in 1996 for St. Louis, playing two years with the Rams and spending his final two seasons with the Kansas City Chiefs. He retired with 132.5 career sacks, tied for 14th on the NFL's all-time official leaderboard. In 2014, the Chargers formally enshrined his legendary status by inducting him into the Chargers Hall of Fame.  With the Chargers, O’Neal compiled 105.5 sacks (franchise record), 517 combined tackles, 22 forced fumbles, and 13 fumble recoveries.