He played college football for the Ole Miss Rebels and was selected by the Tennessee Titans in the second round of the 2019 NFL draft.

[2] As a senior at Starkville High, he recorded 83 receptions for 1,371 yards and 13 touchdowns and led his team to a 6A state championship.

Brown was named first-team All-State by USA Today, The Clarion-Ledger's Dandy Dozen, and the Mississippi Association of Coaches.

[4][5] The San Diego Padres selected Brown as an outfielder in the 19th round of the 2016 Major League Baseball Draft.

[6] Brown participated in extended spring training with the Padres after his freshman and sophomore years at Ole Miss.

[9] As a true freshman at Ole Miss in 2016, Brown played in all 12 games and finished fifth on the team with 29 receptions for 412 yards and two touchdowns.

[11] Brown finished the season with 75 receptions for a school record 1,252 yards and a school-record-tying 11 touchdowns (shared with Laquon Treadwell) in 12 games, leading the team and the SEC.

[12][13] Brown's 2018 junior season was shared with future NFL Pro Bowler DK Metcalf and was highlighted by nine receptions for 212 yards (at the time, second in school history only to his own record the previous year) and a touchdown against Vanderbilt.

Brown again led the team and the SEC in receiving, finishing with a school-record 85 receptions (later passed by Moore) and 1,320 yards (still the record) and six touchdowns.

[23] During Week 4 against the Atlanta Falcons, he caught his first two NFL touchdowns from Marcus Mariota in the 24–10 road victory.

[25] During a Week 12 42–20 victory over the Jacksonville Jaguars, Brown had four receptions for 135 yards and a touchdown as the Titans won.

[30] In the regular-season finale against the Texans, Brown recorded four receptions for 124 yards and a touchdown during the 35–14 road victory to help the Titans clinch a playoff berth.

[34] In three postseason games, Brown totaled five receptions for 64 yards as the Titans' season ended with a 35–24 road loss in the AFC Championship to the Kansas City Chiefs.

[35] During a Tuesday night game in Week 5 against the Buffalo Bills, Brown recorded seven receptions for 82 yards and his first touchdown of the season during the 42–16 victory.

[43] In the Wild Card Round against the Baltimore Ravens, Brown recorded six receptions for 83 yards and a touchdown as the Titans lost 20–13.

[49] In his first game back from injury, Brown had 11 receptions for 145 yards and a touchdown during a 20–17 victory over the San Francisco 49ers.

[65] This included a Week 3 performance against the Washington Commanders in which Brown finished with 175 yards and two touchdowns in a 34-31 overtime victory.

[66] Brown was additionally named NFC Offensive Player of the Month of October for his record-breaking performance.

[69] Due to a sprained knee sustained in the season finale against the Giants, Brown missed the playoffs.

[70] On April 25, 2024, Brown signed a three-year, $96 million contract extension, keeping him with the Eagles through the 2029 season.

Brown stated that reaching out to fellow NFL player Elijah Moore and receiving help allowed him to overcome his struggles.