He played college football for the Alabama Crimson Tide, where he recorded over 1,800 yards with 23 touchdowns as a senior in 2020.

He won two national championships at Alabama prior to being selected by the Eagles tenth overall in the 2021 NFL draft.

[7] In the 2018 College Football Playoff National Championship against Georgia, Smith's only catch of the game was the game-winning 41-yard touchdown reception in an overtime 26–23 victory.

[8][9][10] In the College Football Playoff Semifinal at the Orange Bowl, Smith had six receptions for 104 yards and one touchdown in the 45–34 victory over Oklahoma.

[15] On September 28, Smith set career highs with 274 yards and five touchdowns in a 59–31 victory against Ole Miss.

[18][19] After the season, his teammates Henry Ruggs and Jerry Jeudy forfeited their remaining NCAA eligibility to enter the 2020 NFL draft, where they ended up as first-round picks, but Smith decided to return to Alabama for his senior year.

[24] On November 21, Smith broke the all-time SEC career record for most receiving touchdowns, with two to go along with nine receptions for 144 yards in a 63–3 victory over Kentucky.

Alabama won, 52–24, their sixth title in 12 years, while Smith was named Offensive MVP of the championship game.

[33] Smith became the first wide receiver to win the AP Player of the Year award since its inception in 1998.

[37] His nickname at Alabama was the "Slim Reaper", given to him by his teammates due to his small frame and athletic ability.

Despite his impressive college statistics Smith fell in the draft due to concerns over his raw measurables and that his frame was considered too small to handle playing in the NFL.

[51] Smith had a solid rookie season for the Eagles, as he recorded 64 receptions for 916 yards and five touchdowns.

[53] Like the rest of the Eagles offense, Smith struggled during the team's 31–15 loss in the Wild Card Round to the Tampa Bay Buccaneers, as he ended the game with four catches (on 11 targets) for 60 yards.

[54] In Week 3, against the Washington Commanders, Smith had eight catches for a career-high 169 yards and a touchdown in the 24–8 win.

[58] In the NFC Championship against the San Francisco 49ers, Smith recorded a one-handed 29-yard reception on fourth down on the Eagles' opening drive.