Smith then spent time as a backup for the New York Giants and Los Angeles Chargers before unexpectedly making a career resurgence as the Seahawks' starting quarterback in 2022, earning his first Pro Bowl selection, having his first winning record and playoff berth as a starter, leading the league in completion percentage, and ultimately winning the Comeback Player of the Year award.

His great-uncle, Danny Smith, was a record breaking All-American hurdler at Florida State, and his cousin Mel Bratton was a star running back at Miami in the mid-1980s.

[5] Smith was admitted to Norland Middle School's magnet program, which dedicated two hours per day to arts instruction.

[8] Smith finished his career as the third-best passer in Broward County history, and was named to the ESPN Top 150 prospects list.

Smith got his first start in the season opener against the Coastal Carolina Chanticleers, completing 20 of 27 passes for 216 yards, two touchdowns, and an interception in the 31–0 shutout victory.

After completing 9 of 13 passes and scrambling for 20 yards, Smith found tight end Will Johnson in the corner of the endzone for a touchdown.

Smith completed a pass to wide receiver Jock Sanders in the back of the end zone for a two-point conversion.

[28] Smith finished the 2010 season with 196 passing yards, a touchdown, and an interception in a 23–7 loss to North Carolina State in the Champs Sports Bowl.

[30] With the arrival of new West Virginia football head coach Dana Holgorsen and a new passing-based offensive system, Smith saw his passing numbers improve drastically.

In the fourth game of the season against the #2 LSU Tigers, Smith set school records for completions (38), attempts (65), and passing yards (463) in the 47–21 loss on September 24, 2011.

[31] With 372 passing yards against the Cincinnati Bearcats on November 12, Smith tied a Big East record with his seventh 300-yard game of the season.

[32] Smith set single-season school records for pass completions (291), attempts (448), and yards (3,741) on November 25 in a win against the rival Pittsburgh Panthers.

Smith also became the Big East single-season passing leader with 4,379 yards, breaking Brian Brohm's mark that he set in 2007.

[54] Smith declined to be interviewed by ESPN afterwards and originally planned to return home but later decided to attend the second day of the draft.

[54] Several league executives alleged Smith did not handle the draft process in a professional manner, which caused him to fall out of the first round,[55] while analysts pointed to his late-season decline as a senior at West Virginia, which exposed his flaws, as the primary reason.

[58] Following the selection, General manager John Idzik stated that Smith would compete with incumbent Mark Sanchez in training camp to determine the starting quarterback.

[70] In the next game against the New England Patriots, Smith struggled as he completed 15 of his 35 passes for 214 yards, a touchdown, and three interceptions as the Jets lost on the road by a score of 13–10.

[80] Smith struggled during the Week 8 9–49 road loss to the Cincinnati Bengals as he completed 20-of-30 passes for 159 yards and two interceptions that were returned for touchdowns before being relieved of duties by Matt Simms in the fourth quarter.

Despite this incident, Smith was allowed to start in the next game against the San Diego Chargers, in which he threw for only 27 yards with an interception and was benched for the second half in favor of Michael Vick as the Jets were shut out on the road 31–0.

[100] In the next game, Smith lasted only ten minutes to begin regulation as he completed 2-of-8 passes for five yards and three interceptions against the Bills, and was subsequently benched in favor of Michael Vick.

[101] In the regular-season finale against the Dolphins, Smith led the Jets to a 37–24 road victory, completing 20 of 25 passes for a career-high 358 yards, three touchdowns, no interceptions, and a perfect passer rating.

[104] On August 11, 2015, Smith was involved in an altercation with defensive end IK Enemkpali in the locker room over a $600 unpaid debt.

[113] Making the start in Week 7 against the Ravens, Smith threw for 95 yards and a touchdown until leaving the eventual 24–16 victory with an apparent knee injury.

[117] During a Week 9 51–17 loss to the Los Angeles Rams, Smith came in the game in relief of Eli Manning late in the fourth quarter and finished with only two incomplete passes.

[122] During a Week 6 38–14 road victory over the Cleveland Browns, Smith made his Chargers debut, completing one pass for eight yards.

During the game, Smith became the Seahawks’ single-season passing leader, surpassing Russell Wilson's mark of 4,219 yards set back in 2016.

[163] In Week 18 against the Arizona Cardinals, Smith threw a touchdown and a go-ahead two-point conversion (both to Tyler Lockett) in the fourth quarter in 21–20 win.

He also threw an NFL record seven go-ahead touchdown passes in the fourth quarter and overtime during the season and posted the league's best Total QBR over the final six weeks.

[167] On the road against the 49ers in Week 11, Smith led the Seahawks on an 11-play, 80-yard drive, capped off with a 13-yard touchdown run to put Seattle ahead with 12 seconds left as they won 20–17.

[175][176] Prior to the 2023 NFL season, Smith told Peter King that he had adopted a pescatarian diet, having abstained from eating chicken or beef for most of the year to date.