In his final year in 2006, he had 31 tackles, 10 sacks, and four fumble recoveries at linebacker and ran for 919 yards on 118 carries with 15 touchdowns as a running back, despite missing the first half of the season with a leg injury.

On March 30, 2011, Smith attended USC's pro day and performed all of the combine and positional drills for team representatives and scouts.

[13] Head coach Pete Carroll named Smith the backup weakside linebacker to start the regular season, behind Leroy Hill.

Smith made his first career regular season tackle on Ted Ginn Jr. and stopped him for a ten-yard loss during a punt return in the second quarter.

[15] On November 13, 2011, Smith collected a season-high four solo tackles, forced a fumble, and made his first career sack during a 22–17 victory against the Baltimore Ravens.

[17] He finished his rookie season in 2011 with 16 combined tackles (ten solo), a forced fumble, and a sack while appearing in 12 games with zero starts.

[18] During training camp, Smith competed for a roster spot as a backup outside linebacker against Jameson Konz, Allen Bradford, Heath Farwell, Mike Morgan, and Kyle Knox.

[19][20] Defensive coordinator Gus Bradley retained Smith as a backup outside linebacker, behind Leroy Hill and K. J. Wright, to begin the regular season.

[29] On October 17, 2013, Smith collected a season-high nine combined tackles, a pass deflection, and a sack during a 34–22 win at the Arizona Cardinals in Week 7.

[30] Smith became the starting weakside linebacker in Week 15 after K. J. Wright sustained a fractured foot and was sidelined for the last three games of the regular season.

[30] On December 22, 2013, Smith recorded eight combined tackles, a pass deflection, and made his first career interception during a 17–10 loss to the Arizona Cardinals in Week 16.

Smith intercepted a pass attempt by Cardinals' quarterback Carson Palmer, that was originally intended for running back Andre Ellington, and returned it for a 32-yard gain in the second quarter.

[31] In Week 17, Smith made five combined tackles, a pass deflection, and returned an interception for his first career touchdown in a 27–9 win against the St. Louis Rams.

He intercepted a pass by Kellen Clemens, that was originally thrown to tight end Lance Kendricks, and returned it for a 37-yard touchdown in the first quarter.

[32] Smith finished the 2013 season with 54 combined tackles (34 solo), four passes defensed, a forced fumble, one sack, an interception, and a touchdown in 15 games and eight starts.

On January 11, 2014, Smith started in his first career playoff game and made nine combined tackles during a 23–15 victory against the New Orleans Saints in the NFC Divisional Round.

[5] On February 2, 2014, Smith recorded ten combined tackles (six solo), deflected a pass, recovered a fumble, and returned an interception for a touchdown in the Seahawks' 43–8 victory against the Denver Broncos in Super Bowl XLVIII.

Smith intercepted a pass by quarterback Peyton Manning, that was intended for running back Knowshon Moreno, and returned it for a 69-yard touchdown in the second quarter.

[42] On February 1, 2015, Smith appeared in Super Bowl XLIX, but was held without a stat as the New England Patriots defeated the Seattle Seahawks 28–24.

[47] On October 25, 2015, Smith had a season-high 11 solo tackles, two pass deflections, a sack, and an interception in the Raiders' 37–29 victory against the San Diego Chargers.

Smith intercepted a pass by quarterback Philip Rivers, that was originally intended for wide receiver Stevie Johnson, and returned it for a 27-yard gain during the Chargers' opening drive.

[11][54] Smith entered training camp slated as the starting right outside linebacker, but saw competition from rookie first round pick Reuben Foster.

[55] On August 7, 2017, the San Francisco 49ers officially placed Smith on injured reserve after an MRI determined he had suffered a torn pectoral muscle.

[63] He appeared in 15 games with 4 starts, collecting 72 tackles (fourth on the team), one sack, one interception, 2 passes defensed and one forced fumble.

It started to affect him around the time of the 2009 Rose Bowl, where he began losing a few pounds of body weight each week because food would get stuck in his esophagus and he would have to throw it up.

Smith underwent a surgical procedure called a Heller myotomy which helped somewhat, but he still has dietary restrictions that force him to eat very slowly.