Larry played free safety in the NFL with the St. Louis Cardinals. He played his entire 13-year career with them and remained on the team's payroll until 2003, long after the team moved to Arizona in 1988 in the front office.
Despite his skill and adaptability, Wilson's small size (he was only six feet tall) resulted in him not being selected until the 7th round of the 1960 draft by the Chicago Cardinals. The draft was held in November 1959, and the franchise moved to St. Louis before the start of the 1960 season.
Wilson was named All-Pro six times in his career and represented the Cardinals on eight Pro Bowl teams. During 1966, he had at least one interception in seven consecutive games, en route to a 10-pick season that led his league. Fellow Idahoan Jerry Kramer, a guard for the Green Bay Packers and author of Instant Replay, called Wilson "the finest football player in the NFL." Kramer described Wilson's play during an October 30, 1967 game, "...he fired up their whole team ... (h)is enthusiasm was infectious."Wilson is renowned for not only playing, but intercepting a pass, with casts on both hands due to broken wrists. On the September 18, 2006 edition of SportsCenter, Mike Ditka challenged Terrell Owens' toughness by not playing for 2–4 weeks due to a broken finger. He cited Wilson's interception with casts on both hands as proof of a tougher football player. He ended his career with 52 career picks for 800 yards and five touchdowns.
Wilson retired after the 1972 season. He is one of the few players to have played in the NFL for at least 10 years without having taken part in an official playoff game. The closest he came to postseason play was in 1964, when the Cardinals played in and won the Playoff Bowl, a postseason third-place game. It was one of only five winning seasons the Cardinals had during his 13-year career.
Wilson was inducted into the Pro Football Hall of Fame in 1978, making him one of the few Hall of Famers to have never played in the postseason. In 1999, he was ranked number 43 on The Sporting News' list of the 100 Greatest Football Players, making him the highest-ranked player to have played a majority of his career with the Cardinals. The team has also retired his uniform number 8. In 2007, NFL Network ranked him ninth on its list of the "Top 10 Draft Steals" in NFL history. Wilson was named to the NFL 75th Anniversary All-Time Team in 1994 and was named to the NFL 100th Anniversary All-Time Team in 2019.