Pre-draft Playing as a defensive end at Missouri, Smith was considered a "DE/OLB prospect" by most NFL scouts and was considered a strong edge run defender as 4–3 end or 3–4 linebacker. Many scouts had compared him to
DeMarcus Ware. Prior to the
2011 NFL draft, Smith was projected to be selected in the mid-late first round by mock draft analysis.
San Francisco 49ers 2011 season The
San Francisco 49ers drafted Smith in the first round with the seventh overall pick. Smith did not start but made his NFL debut in the season-opening 33–17 victory over the
Seattle Seahawks, recording a pass deflection. Three weeks later against the
Philadelphia Eagles, Smith recorded five tackles and his first 1.5
sacks on
Michael Vick in the narrow 24–23 victory. Over the next two weeks, Smith would win the
Pepsi NFL Rookie of the Week in victories against the
Tampa Bay Buccaneers and
Detroit Lions. After a strong October, Smith became the first 49ers player since linebacker
Patrick Willis in
2007 to earn the NFL Rookie of the Month award; Smith recorded 13 tackles and 6.5 sacks, including one that forced a
safety as he helped the 49ers to a 6–1 record. During a Week 15 20–3 victory over the
Pittsburgh Steelers on
Monday Night Football, Smith recorded four tackles and 2.5 sacks. He also surpassed
Charles Haley for the 49ers record for most sacks by a rookie in a single season with 13.0 sacks. Smith finished his rookie year with 37 total tackles, 14 sacks, four pass deflections, two forced fumbles, and a fumble recovery in 16 games. He was half a sack shy of tying the all-time rookie sack record held by defensive end
Jevon Kearse despite not starting a single game in his rookie season. Smith was named Defensive Rookie of the Year by Pro Football Writers of America, and finished second to
Von Miller for the
Associated Press NFL Defensive Rookie of the Year Award. Smith was named to the NFL All-Rookie Team.
2012 season After being used only as a situational pass rusher throughout his rookie year, Smith became a full-time starter in 2012. During the season-opening 30–22 road victory over the
Green Bay Packers, Smith recorded four tackles and sacked
Aaron Rodgers once. In the next game against the
Detroit Lions, Smith recorded six tackles and 1.5 sacks as the 49ers won by a score of 27–19. Two weeks later, he had two sacks as the 49ers shut out the
New York Jets on the road by a score of 34–0. During a Week 11 32–7 victory over the
Chicago Bears, Smith recorded seven tackles, 5.5 sacks, and two fumble recoveries. He was named NFC Defensive Player of the Week due to his spectacular performance. In the next game against the
New Orleans Saints, Smith surpassed
Reggie White as the fastest player in league history to record his 30th career sack, doing so in 27 games. Smith was named NFC Defensive Player of the Month for November. The following week against the
St. Louis Rams, Smith broke another of White's records by recording 31.5 sacks in his first two seasons. In that same game, Smith tied
Fred Dean's franchise record of 17.5 sacks in a season. During a Week 15 41–34 road victory over the
New England Patriots, Smith recorded a tackle, a pass deflection, and his first NFL interception off of
Tom Brady. Smith was named to the Pro Bowl and earned First Team All-Pro honors. in
Super Bowl XLVII Smith finished his second professional season with 19.5 sacks, 66 tackles, three forced fumbles, an interception, and a pass deflection in 16 games and starts. He broke
Cedrick Hardman's 49er's franchise record of 18 sacks in one season, which Hardman set in 1971, a 14-game NFL season. The 49ers went on to appear in
Super Bowl XLVII. In the game, Smith had two combined tackles as the 49ers narrowly lost to the
Baltimore Ravens by a score of 34–31. On the
NFL Network's
NFL Top 100 Players of 2013 ranking, players voted Smith as the seventh-best player in the league entering the 2013 season, which made him the second-highest-ever debut and second-highest defensive player on the list, both behind
J. J. Watt. Smith was voted the San Francisco 49ers MVP in 2012.
2013 season Smith got off to a fast start in 2013, recording 18 tackles and 4.5 sacks in the first three games. However, on September 20, he was involved in a single-vehicle accident in
San Jose, California. He was subsequently arrested on suspicion of driving under the influence and possession of marijuana. After a Week 3 27–7 loss to the
Indianapolis Colts, Smith voluntarily entered a rehabilitation facility, to be put onto the non-football injury list with an indefinite leave of absence. Smith missed five games while in rehabilitation. He returned to the team in Week 10 against the
Carolina Panthers, but in a backup role, and did not start a game until Week 13 against the
St. Louis Rams. Smith ended the season strong, finishing with 34 tackles and 8.5 sacks in 11 games and eight starts. Despite his limited playing time, Smith was ranked #33 in the
NFL Top 100 Players of 2014.
2014 season Smith served a nine-game suspension for violating the NFL's substance abuse and personal conduct policies. He was reinstated in Week 11. On August 7, 2015, following an arrest for his third DUI, Smith was released by the 49ers.
Oakland Raiders 2015 season On September 11, 2015, Smith signed a one-year contract with the
Oakland Raiders. Smith made his Raiders debut in the season-opening loss to the
Cincinnati Bengals and recorded two tackles. Two weeks later against the
Cleveland Browns, Smith got his first start of the year and finished the 27–20 road victory with two solo tackles and two pass deflections. In the next game against the
Chicago Bears, he recorded a season-high six tackles and his first sack of the season as the Raiders narrowly lost on the road by a score of 22–20. Smith played his last game of the season in Week 10 against the
Minnesota Vikings and finished the 30–14 loss with three tackles and a sack. Two days later, the NFL issued Smith a one-year suspension due to a hit-and-run incident that occurred on August 6, 2015. Smith finished his first season with the Raiders with a total of 28 tackles and 3.5 sacks in nine games and seven starts.
2016 and 2017 seasons On April 4, 2016, Smith re-signed with the Raiders. On October 27, he applied for reinstatement. However, no reinstatement occurred, resulting in Smith sitting out the entire 2016 and 2017 NFL seasons. Following an alleged domestic violence incident, the Raiders released Smith on March 5, 2018.
Dallas Cowboys On March 14, 2020, it was reported Smith was "in the process" of applying for reinstatement from an indefinite league suspension. He signed a one-year contract with the
Dallas Cowboys on April 2, after impressing with his conditioning and size (287 pounds). On May 26, Smith was conditionally reinstated by the NFL and was cleared to take place in the Cowboys' virtual off-season program. During the season-opening 20–17 road loss to the
Los Angeles Rams on
Sunday Night Football, Smith played in a regular season game for the first time since November 15, 2015. He tied for a team-high 11 tackles (one for loss), had his first sack of the season, and had two quarterback hits on
Jared Goff. Two weeks later against the
Seattle Seahawks, Smith sacked
Russell Wilson thrice, had two tackles for loss, four quarterback hits, and a pass deflection in the 38–31 road loss. After posting four sacks in the first three games, Smith's production decreased considerably in the following weeks (tallying only one more sack) and he also was limited with a knee injury. His time on the field was reduced in favor of playing defensive end
Randy Gregory. During a Week 14 30–7 road victory over the
Cincinnati Bengals, Smith recovered a fumble lost by running back
Trayveon Williams and returned it 78 yards (fifth longest in franchise history) for his first NFL touchdown. Smith finished the 2020 season with 53 tackles (four for loss), five sacks (second on the team), 35 quarterback pressures (second on the team), two pass deflections, and two fumble recoveries in 16 games and starts.
Seattle Seahawks On April 15, 2021, Smith signed a one-year contract with the
Seattle Seahawks. On August 11, he was released.
Retirement Following his release from jail on October 24, 2023, Smith stated that he was "done with (foot)ball". ==NFL career statistics==