He committed to the University of Oklahoma to play college football under head coach Bob Stoops.

[4][5] As a true freshman at the University of Oklahoma in 2012, Shepard played in all 13 games with four starts and had 45 receptions for 621 yards and three touchdowns.

[19] On September 2, against Tennessee, he caught a five-yard touchdown from Baker Mayfield with only 40 seconds remaining to help force overtime.

[25][26] Going into the regular season, Shepard was named a starting wide receiver, along with Odell Beckham Jr.

[27] The following week, Shepard caught a season-high eight passes for 117 receiving yards in a 16–13 victory over the New Orleans Saints.

[29] On November 6, 2016, he continued to emerge as a promising receiver after he made three receptions for 50 yards and caught a 23-yard touchdown pass in a victory over the Philadelphia Eagles.

[30] The following game, Shepard caught five passes for 42 receiving yards and a touchdown in a 21–20 win over the Cincinnati Bengals.

[32] In a Week 16 match-up against the Philadelphia Eagles, Shepard made seven catches for 61 yards and a touchdown as the Giants lost 24–19.

In his playoff debut, he had four receptions for 63 receiving yards in the 38–13 Wild Card Round loss to the Green Bay Packers.

[36] Shepard started the 2017 season off with nine receptions for 67 receiving yards combined in the first two games against the Cowboys and Detroit Lions.

[40] During Week 10 against the San Francisco 49ers, Shepard had a career high eleven receptions for 142 receiving yards as the Giants lost 31–21.

[48] In Week 3 against the Tampa Bay Buccaneers, Shepard caught seven passes for 100 yards and a touchdown as the Giants won 32–31.

[49] In Week 15 against the Miami Dolphins, Shepard caught a season high nine passes for 111 yards in the 36–20 win.

[51] During Week 2 against the Bears, Shepard left the game in the second quarter with a toe injury and did not return.

[55] In Week 1, Shepard finished the game with seven receptions for 113 yards and a touchdown in a 27–13 loss to the Denver Broncos.