He became part of an effective receiving tandem alongside Adam Thielen, with his highlights including catching the "Minneapolis Miracle" pass during the 2017–18 NFL playoffs.

Diggs attended Our Lady of Good Counsel High School in Montgomery County, Maryland, where he played football and ran track.

The members of that relay consisted of fellow NFL players Kendall Fuller, Blake Countess, and a National Champion 400m sprinter Sean Sutton.

[17] He totaled 152 yards on a season-high 11 receptions, including a 66-yard touchdown against Boston College, earning ACC Rookie of the Week for the third time.

[30] In his first game since suffering a lacerated kidney on November 1, Diggs was one of the few bright spots during Maryland's 45–21 loss to Stanford; he had 10 catches for 138 yards, including a 26-yard catch-and-run that helped set up the Terps' first touchdown.

[32][33] Diggs (6 ft 0 in (1.83 m), 195 pounds (88 kg)) ran the 40-yard dash in 4.46 seconds at the 2015 NFL Combine and stood on those numbers at his Pro Day.

In the Vikings' 23–20 win over the Chicago Bears in Week 8, Diggs recorded his fourth consecutive game with at least five catches and 80 yards.

[41] On a crucial third-down play with only 2:00 left, Diggs caught a short pass from Teddy Bridgewater at the 30-yard line, then he spun around cornerback Sherrick McManis and turned upfield over his right shoulder with open space in front of him.

In Week 9, Diggs led the team in receptions (3) and yards (42) and recovered a fumble by Adrian Peterson in the Vikings' overtime win over the St. Louis Rams.

During the game, he had an unsportsmanlike conduct penalty due to his celebration of spinning the ball into Falcons' safety Charles Godfrey after his 16-yard reception in converting a 3rd & 8.

On his second score, Bridgewater found him on a short crossing pattern across the middle on third down and Diggs accelerated towards the sidelines, juked one defender and carried another on his back for seven yards to complete a 33-yard catch and run that put the Vikings up 24–7.

[47] On January 19, 2016, Diggs was named to the Pro Football Writers of America's (PFWA) 2015 NFL All-Rookie team.

In the season opening game at the Tennessee Titans on September 11, Diggs led the Vikings with seven catches for 103 yards on nine targets.

2 wide receiver behind Charles Johnson, Diggs still led the team in targets, receptions, and yards as the Vikings were forced to throw more than expected with the Titans bottling up the running game.

With the Packers stacking the box to stop the running game, Diggs exploited man-to-man coverage from second-year cornerback Damarious Randall and became the focal point of the offense, playing a key role in the Vikings' 17–14 win over the Packers as he finished the game with career-highs in both catches with nine and receiving yards with 182.

[58] On September 11, 2017, in the season opener against the New Orleans Saints on Monday Night Football, Diggs caught seven receptions for 93 yards and two touchdowns.

[59] During Week 3 against the Tampa Bay Buccaneers, Diggs posted an impressive performance with 173 receiving yards and two touchdowns as the Vikings won by a score of 34–17.

[61] In the Week 5 victory against the Bears, Diggs would only record a single catch for four yards, leaving the field early with a groin injury.

[65] The Vikings finished the 2017 season with a 13–3 record, clinching the NFC North division and a bye in the first round of the playoffs.

[71][72] During Week 1, Diggs caught Kirk Cousins's first touchdown pass as a Viking in a 24–16 win over the San Francisco 49ers.

[81] During the Week 6 38–20 win over the Eagles, Diggs caught seven passes for an NFL-best[82] 167 yards and career-best three touchdowns, becoming the first Viking to accomplish the feat since Marcus Robinson in 2005.

[98] The following week, on Sunday Night Football against the Pittsburgh Steelers, Diggs caught ten passes (his fourth such game on the year), for 130 yards and a touchdown during the Bills' 26–15 win.

[106][107] In the Wild Card Round of the playoffs against the Indianapolis Colts, Diggs recorded six catches for 128 yards and a touchdown during the 27–24 win.

[109] In the AFC Championship against the Chiefs, Diggs, playing with a torn oblique,[110] recorded six catches for 77 yards during the 38–24 loss.

[113] During the offseason, the Bills signed veteran receiver Emmanuel Sanders to complement Diggs in the passing game.

[116] Diggs was named to the Pro Bowl for the second consecutive year,[117] finishing the season with 1,225 receiving yards and a career-high 10 touchdowns.

He would then catch a 36-yard pass from Josh Allen two-and-a-half minutes later on Buffalo's ensuing drive to help set up a Tyler Bass game-winning field goal.

[126] During the Bills' Divisional-round playoff loss to the Cincinnati Bengals, Diggs was seen on the telecast visibly upset while talking with Allen on the sidelines during the fourth quarter and quickly left the locker room after the game.

[131] In the 2023 season, Diggs finished with 107 receptions for 1,183 yards and eight touchdowns,[129] though his production trailed off towards the end of the year, coinciding with the Bills' re-emphasis on their rushing attack.

[135] NFL insider Ian Rapoport reported that the Texans restructured Diggs' four-year contract extension from the Bills in 2022 with two years remaining into a one-year, $22.52 million deal.