Pre-draft Coming out of Colorado, Witherspoon was projected to be a second or third round pick by the majority of NFL draft experts and scouts. He received an invitation to the
NFL Combine and performed nearly every combine drill, but opted to skip the
bench press. On March 8, 2017, Witherspoon chose to participate at Colorado's
pro day long with,
Chidobe Awuzie,
Tedric Thompson,
Sefo Liufau, and ten other prospects. All 32 NFL teams had team representatives and scouts present. He had five private workouts and visits with the
Indianapolis Colts,
New Orleans Saints,
Philadelphia Eagles,
San Francisco 49ers, and
Seattle Seahawks. Witherspoon was ranked the 14th best cornerback prospect in the draft by NFLDraftScout.com.
San Francisco 49ers 2017 , 2017 The 49ers selected Witherspoon in the third round (66th overall) of the
2017 NFL draft. He was the 11th cornerback selected in the draft. On May 12, 2017, the 49ers signed Witherspoon to a four-year,
$3.88 million
contract that included an initial
signing bonus of $973,572. Throughout
training camp, Witherspoon competed against
Dontae Johnson,
Rashard Robinson, and
Keith Reaser to earn a role as a starting cornerback following the departure of
Jimmie Ward. Head coach
Kyle Shanahan named Witherspoon a backup cornerback to begin the season and listed him as the fifth cornerback on the depth chart, behind Johnson, Robinson,
K'Waun Williams, and Reaser. Witherspoon was inactive as a healthy scratch for the first four games (Weeks 1–4) of the season. On September 16, 2017, the 49ers released Reaser, but opted to sign
Asa Jackson to the active roster with Witherspoon remaining inactive. Heading into Week 5, he had surpassed Asa Jackson on the depth chart and was promoted to the fourth cornerback on the depth chart. On October 8, 2017, Witherspoon made his professional regular season debut, but was limited to a solo tackle during a 26–23 overtime road loss to the
Indianapolis Colts. Entering Week 8, defensive coordinator
Robert Saleh promoted Witherspoon to the starting cornerback after Rashard Robinson was benched following disappointing performances and repetitive penalties. Witherspoon earned his first career start in Week 8 against the
Philadelphia Eagles, recording three solo tackles, a pass deflection, and his first career interception on a pass attempt thrown by
Carson Wentz to wide receiver
Mack Hollins during the 33–10 road loss.
Pro Football Focus graded Witherspoon the best player on the 49ers during the matchup against the Eagles and credited him with allowing three receptions on eight targets. Two days later, the 49ers traded Robinson to the
New York Jets. Head coach
Kyle Shanahan stated that Witherspoon would be the starting cornerback, opposite Dontae Johnson, moving forward and his development was one of the key factors in their decision to trade Robinson. He surpassed
Leon Hall,
Greg Mabin, and K'Waun Williams on the depth chart. During Week 16 against the
Jacksonville Jaguars, Witherspoon had three combined tackles (two solo), set a season-high with two pass deflections, and also intercepted a pass by
Blake Bortles to wide receiver
Keelan Cole in the 44–33 victory. In the regular season finale against the
Los Angeles Rams, Witherspoon collected a season-high tying four solo tackles and a pass deflection during the 34–13 road victory. Witherspoon finished his rookie year with 32 combined tackles (28 solo), seven pass deflections, and two interceptions in 12 games and nine starts.
2018 Throughout training camp, Witherspoon competed against K'Waun Williams, Jimmie Ward,
D. J. Reed,
Emmanuel Moseley,
Tarvarius Moore, and
Tarvarus McFadden to be the No. 2 starting cornerback. Head coach Kyle Shanahan named Witherspoon and
Richard Sherman the starting cornerbacks to begin the regular season. During a Week 3 38–27 road loss to the
Kansas City Chiefs, Witherspoon collected a season-high five solo tackles. During Week 15 against the
Seattle Seahawks, he had a solo tackle before leaving the eventual 26–23 overtime victory in the third quarter with a knee injury. On December 18, 2018, Witherspoon was placed on
injured reserve. Witherspoon finished his sophomore professional season with 37 combined tackles (30 solo), four pass deflections, and a fumble recovery in 14 games and 12 starts.
2019 Witherspoon entered training camp projected to be the No. 2 starting cornerback. He competed against
Jason Verrett, K'Waun Williams, and D. J. Reed. Head coach Kyle Shanahan named Witherspoon a starting cornerback to begin the season and paired him with Richard Sherman. During the season-opening 31–17 road victory over the
Tampa Bay Buccaneers, Witherspoon had two solo tackles, a season-high with three pass deflections, and intercepted a pass thrown by
Jameis Winston to running back
Dare Ogunbowale and returned it 25 yards for his first career touchdown. Witherspoon was inactive due to a foot injury for six consecutive games (Weeks 5–10). In the regular season finale against the Seahawks, he recorded a season-high five solo tackles and two pass deflections during the 26–21 road victory. Witherspoon finished the regular season with 28 combined tackles (24 solo), a career-high nine pass deflections, an interception, and a touchdown in 10 games and eight starts. The 49ers finished the season atop the
NFC West with a 13–3 record and clinched the #1-seed in the playoffs. In the Divisional Round against the
Minnesota Vikings, Witherspoon was demoted to a backup role to
Emmanuel Moseley after a poor performance. The 49ers went on to reach
Super Bowl LIV, but lost 31–20 to the Chiefs. Witherspoon finished the Super Bowl with one tackle.
2020 During training camp, Witherspoon competed against
Emmanuel Moseley to be the No. 2 starting cornerback. Head coach Kyle Shanahan named him a backup and listed Witherspoon as the fourth cornerback on the depth chart to begin the season, behind Richard Sherman, Moseley, and
K'Waun Williams. Witherspoon was inactive for two games (Weeks 3–4) after injuring his hamstring. After Week 8, Witherspoon was placed at the bottom of the depth chart as the eighth cornerback, behind Jason Verrett, Emmanuel Moseley, K'Waun Williams,
Jamar Taylor, Dontae Johnson, and
Ken Webster. Witherspoon was inactive as a healthy scratch for three games (Weeks 9, 10, and 12). Entering Week 13, Witherspoon was promoted to being the fourth cornerback on the depth chart after both
Emmanuel Moseley and
K'Waun Williams suffered injuries. During a Week 15 41–33 road loss to the
Dallas Cowboys, Witherspoon earned his second start of the season, appearing as a nickelback and recorded a solo tackle and a season-high two pass deflections. In the next game against the
Arizona Cardinals, Witherspoon set a season-high with seven solo tackles, made one pass deflection, and had his first career interception on a pass attempt thrown by
Kyler Murray to wide receiver
Christian Kirk late in the fourth quarter to help secure a 20–12 road victory for the 49ers. Witherspoon finished the 2020 season with 20 combined tackles (17 solo), four pass deflections, and an interception in 11 games and four starts.
Seattle Seahawks On March 19, 2021, the
Seattle Seahawks signed Witherspoon to a one-year, $4 million contract that was fully guaranteed and included an initial signing bonus of $2.5 million. Defensive coordinator
Ken Norton Jr. held an open competition between
D. J. Reed,
Tre Brown,
Tre Flowers,
Damarious Randall, and
Pierre Desir in order to select their starting cornerbacks.
Pittsburgh Steelers 2021 On September 3, 2021, the
Pittsburgh Steelers executed a trade and agreed to send their
2023 fifth-round pick (151st overall) to the
Seattle Seahawks in return for Witherspoon. Upon his initial arrival, head coach
Mike Tomlin listed Witherspoon as the sixth cornerback on the depth chart to begin the season, behind
Joe Haden,
Cameron Sutton,
James Pierre,
Arthur Maulet, and
Justin Layne. Witherspoon was inactive for the season-opening 23–16 road victory over the
Buffalo Bills. He remained inactive as a healthy scratch for the next seven games (Weeks 3–10). Going into Week 11, defensive coordinator
Keith Butler promoted Witherspoon and listed him as the fourth cornerback on the depth chart after Joe Haden injured his foot and remained inactive for four games. During Week 13, Witherspoon had a season-high five solo tackles and a pass deflection in a narrow 20–19 victory over the
Baltimore Ravens. In the next game against the Vikings on Thursday Night Football, he recorded four solo tackles, three pass deflections, and set a new career-high with two interceptions on pass attempts thrown by
Kirk Cousins during the 36–28 road loss. Three weeks later against the
Cleveland Browns on
Monday Night Football, Witherspoon tied his season-high with three pass deflections and also set a new career-high with his third interception of the season on a pass by
Baker Mayfield to wide receiver
Donovan Peoples-Jones in the 26–14 victory. Witherspoon finished the 2021 season with 15 combined tackles (14 solo), nine pass deflections, and a career-high three interceptions in nine games and three starts.
2022 On March 25, 2022, the Steelers signed Witherspoon to a two-year, $8 million contract extension with an initial
signing bonus of $2.96 million. He entered training camp projected to be the No. 3 cornerback on the depth chart under the Steelers' new defensive coordinator
Teryl Austin. Austin was hired to replace Keith Butler after he chose to retire. Head coach
Mike Tomlin named Witherspoon the No. 1 starting cornerback to begin the season in lieu of
Levi Wallace and paired him with
Cameron Sutton. Witherspoon started during the season-opener at the
Cincinnati Bengals and had a season-high with eight combined tackles (six solo), a pass deflection, and his lone interception of the season on a pass by
Joe Burrow to wide receiver
Tyler Boyd in the fourth quarter of the 23–20 overtime road victory. Two weeks later against the Browns on
Thursday Night Football, Witherspoon recorded five combined tackles (four solo) and a pass deflection before leaving the eventual 29–17 road loss with a hamstring injury. He was inactive for the next four games (Weeks 4–7) due to his injury. During a Week 8 35–13 road loss to the Eagles, Witherspoon returned from injury and made five solo tackles before head coach Mike Tomlin benched him for the second half after Witherspoon gave up two touchdowns. On December 3, 2022, the Steelers officially placed Witherspoon on injured reserve due to his hamstring injury. He finished the 2022 season with 20 combined tackles (17 solo), two pass deflections, and an interception in 13 games and five starts. On May 17, 2023, Witherspoon was released.
Los Angeles Rams On June 29, 2023, the
Los Angeles Rams signed Witherspoon to a one-year, $1.08 million contract. He recorded his first interception as a Ram in a loss to the
Cincinnati Bengals on September 25. On September 11, 2024, Witherspoon was signed to the Rams' practice squad after going unsigned during the offseason. On October 22, the Rams promoted Witherspoon to their active roster and signed him to a one-year, $1.12 million contract. Witherspoon dove to catch a game-winning interception against
Kyler Murray and the
Arizona Cardinals on December 28. Witherspoon's play sealed a key win for the Rams, as it helped them clinch the NFC West division crown. On March 19, 2025, it was announced that Witherspoon agreed to a one-year contract to return for his third season with the Rams. He started at cornerback in the Rams' first two games, but suffered a
broken scapula in Week 2 and was placed on injured reserve. Witherspoon was activated on November 29. However, he re-broke his scapula during the Wild Card Round against the Panthers and was placed on season-ending injured reserve on January 12, 2026.
Washington Commanders On March 26, 2026, Witherspoon signed a one-year contract with the
Washington Commanders. ==NFL career statistics==