Witherspoon, selected fifth overall in the 2023 NFL Draft, quickly made a name for himself with a breakout performance in Week 4 against the New York Giants, just his third game played. He recorded a 97-yard interception returned for a touchdown, the second-longest in franchise history. Witherspoon became the first player in NFL history to record two or more sacks and an interception return of over 95 yards in the same game. By the end of his rookie season, Witherspoon tallied 16 passes defensed, one interception, one forced fumble, 79 total tackles, and three sacks. He was named to the PFWA All-Rookie Team, earned a Pro Bowl selection, and received votes for Defensive Rookie of the Year.