He played college football for the Notre Dame Fighting Irish and was selected by the Vikings in the first round of the 2012 NFL draft with the 29th overall pick.

He was invited to attend the 2012 NFL Combine as a free safety and completed the entire workout and every positional drill.

Smith was satisfied enough with his combine performance that he chose to only partake in positional drills at Notre Dame's Pro Day.

[17] On April 26, 2012, the Minnesota Vikings selected Smith in the first round (29th overall) of the 2012 NFL draft after trading up with the Baltimore Ravens.

[21] Entering training camp, Smith competed against Jamarca Sanford and Andrew Sendejo for the starting free safety spot.

In Week 13 against the Green Bay Packers, Smith recorded 11 combined tackles and intercepted a pass thrown by Aaron Rodgers as the Vikings lost 23–14.

In a Week 16 matchup against the Houston Texans, he decided seven solo tackles and made his first career sack on Matt Schaub, as the Vikings won 23–6.

In the season-opener against the Detroit Lions, Smith made a season-high ten combined tackles and deflected a pass as the Vikings lost 34–24.

[30] On October 18, 2013, Smith was placed on injured-reserve after suffering an injury to his left foot during a Week 6 loss to the Carolina Panthers.

Smith started only seven games in the 2013 season due to his foot injury and made 58 combined tackles and two interceptions.

[35] The following week, in a Thursday Night Football game against the Packers, Smith intercepted a pass thrown by Matt Flynn in a 42–10 loss.

[38] He started all 16 games and finished his first year under head coach Mike Zimmer with 92 combined tackles, nine deflected passes, three sacks, five interceptions, and a touchdown.

[41] In Week 16, Smith racked up five combined tackles and intercepted a pass thrown by Eli Manning that he returned for a 35-yard touchdown in the Vikings' 49–17 win over the New York Giants.

In a Week 11 matchup against the Cardinals, Smith recorded a season-high ten combined tackles and sacked Carson Palmer in a 30–24 victory.

[27] Smith missed Weeks 14 and 15 with a high ankle sprain that was initially thought to possibly be a season-ending injury that required surgery.

[49] On December 20, 2016, the NFL announced that Smith and fellow Vikings Xavier Rhodes and Cordarrelle Patterson had been voted to the 2017 Pro Bowl.

[52] Two weeks later, in a Monday Night Football game against the Bears, Smith intercepted rookie quarterback Mitch Trubisky to seal a 20–17 win.

[58] In week 5 against the Eagles, Smith had 4 tackles and sealed the game with a big hit late in the 4th quarter to prevent a third-down conversion.

After recording 84 tackles, three sacks, and three interceptions on the season, Smith was selected to a fourth straight Pro Bowl as well as being named a Second-team All-Pro.

[61] In Week 14 against the Lions, Smith intercepted a pass thrown by rookie quarterback David Blough that was intended for wide receiver Kenny Golladay in the 20–7 win.

[62] In Week 15 against the Los Angeles Chargers, Smith intercepted a pass thrown by Philip Rivers and recovered a fumble forced by Danielle Hunter on running back Melvin Gordon during the 39–10 win.

[63] In Week 16 against the Green Bay Packers, Smith forced a fumble on wide receiver Davante Adams that was recovered by teammate Eric Kendricks during a 23–10 loss.

[72] In Week 10 against the Bears on Monday Night Football, Smith recorded another interception, this time off a pass thrown by Nick Foles during the 19–13 win.

[75] In the 2020 season, he made 16 starts and recorded .5 sacks, 89 total tackles (54 solo), five interceptions, and ten passes defended.

[88][89][90] In a 27–22 win over the Jets in Week 13, Smith recorded his fifth interception of the season off a pass thrown by Mike White, tying his single-season career high.

[91] In 14 appearances and starts in the 2022 season, Smith had 85 total tackles (66 solo), five interceptions, ten passes defended, and one forced fumble.