He played college football for Ohio State and was selected by the New Orleans Saints in the second round of the 2016 NFL draft.

[6] Thomas attended Fork Union Military Academy for a year after high school and was roommates with fellow Ohio State teammate Cardale Jones.

[28][29] The Saints named Thomas one of their starting wide receivers, along with Brandin Cooks, for the season opener against the Oakland Raiders.

[30] On September 26, 2016, he caught his first NFL touchdown on a three-yard pass from Drew Brees during the second quarter of a Monday Night Football matchup against the Atlanta Falcons.

[32] During a Week 9 road game against the San Francisco 49ers, Thomas caught two touchdowns and made five catches for 73 yards, as the Saints routed the 49ers by a score of 41–23.

[33] On November 27, Thomas caught nine passes for 108 yards and tied his season-high of two touchdown receptions in a 49–21 win over the Los Angeles Rams.

[38] In his second season, Thomas came into the year as the Saints' number one receiver after Brandin Cooks was traded to the New England Patriots.

[42] Thomas appeared in his first career playoff game on January 7, 2018, against the division rival Carolina Panthers in the Wild Card Round.

[50] Prior to a Week 9 matchup against the Rams, Thomas engaged in an online feud with ex-Saints receiver Brandin Cooks following his departure.

Upon scoring, Thomas paid tribute to former Saints wide receiver Joe Horn by recreating his famous cell phone touchdown celebration in an effort to simultaneously taunt the Rams,[53] which drew a 15-yard unsportsmanlike conduct penalty and he was later fined $30,000 by the league office.

Thomas had four receptions for 36 yards as the Saints' comeback was cut short by a controversial hit during the fourth quarter.

[65] During a critical play in overtime, the score was tied 23–23 as Brees attempted to target Thomas for a crucial pass to keep their drive alive.

Brees was charged by Rams' defensive end Dante Fowler as he threw the ball to Thomas, who was promptly beaten to the catch by Rams' safety John Johnson who mockingly celebrated Thomas' "horse-saddle" as a retaliatory action for his gesture earlier in the season.

[69] During the season-opener against the Houston Texans on Monday Night Football, Thomas caught 10 passes for 123 yards in the narrow 30–28 victory.

[71][72] Thomas rebounded strongly the following week against the Seattle Seahawks, as he caught five passes for 54 yards and scored his first touchdown of the season in the 33–27 road victory.

[80] In the next game against the Indianapolis Colts on Monday Night Football, Thomas caught 12 passes for 128 yards and a touchdown during the 34–7 win.

[83] In the NFC Wild Card Round against the Vikings, Thomas caught seven passes for 70 yards during the 26–20 overtime loss.

[88] In Week 1 against the Buccaneers, Thomas recorded three catches for 17 yards before exiting the game due to a high ankle sprain.

[92] Thomas made his return from injury in Week 9 against the Tampa Bay Buccaneers on Sunday Night Football.

[97] In the Wild Card Round against the Bears, Thomas recorded five catches for 73 yards and his first touchdown reception of the season during the 21–9 win.

[101] Thomas returned from his injury in Week 1 against the Falcons, where he caught five passes for 57 yards, and two touchdowns in the 27–26 comeback win.

[109] As a free agent, Thomas was suspended one game by the NFL for violating the personal conduct policy, relating to a legal incident he had in November 2023.

It was revealed that Thomas was involved in an altercation with a man doing construction work and allegedly threw a brick at the windshield of a truck, leading to his arrest.