Lockett entered his senior season as a preseason All-Big 12 selection as well as a Walter Camp Award, Maxwell Award, Paul Hornung Award, and Biletnikoff Award watchlist candidate. On September 25, he was named one of 62 FBS semifinalists for the William V. Campbell Trophy. He posted his first 100-yard game of the season against Iowa State on September 6, in Kansas State’s second game when he tallied 136 receiving yards on 6 receptions. On September 18, he was named one of 30 candidates for the Senior CLASS Award. On September 27, Lockett posted two 50-plus-yard punt returns including a 58-yard touchdown against UTEP. On September 29, Lockett earned his sixth career Big 12 player of the week recognition when he was named Big 12 Special Teams Player of the Week. The following week, he posted 12 receptions for 125 yards and 2 touchdowns against Texas Tech on October 4, and he added 103 yards on 8 receptions against Texas on October 25. On October 30, he earned an $18,000 postgraduate scholarship as one of 16 finalists for the Campbell Trophy. On November 8, he posted 196 yards and a touchdown on 11 receptions against #6 TCU. The effort boosted Lockett’s career receiving yardage total to 3,073 yards, surpassing his father’s school record total of 3,032 set in 1996. Then, he was named as one of 10 finalists for the Senior CLASS Award and one of 10 semi-finalists for the Biletnikoff Award. On November 20, he was recognized as a first team Academic All-Big 12 honoree. Lockett had 10 receptions for 196 yards and a 43-yard punt return touchdown against West Virginia on November 20 and 9 receptions for 119 yards and 2 touchdowns against Kansas on November 29. In the Kansas–Kansas State rivalry game, Lockett passed his father’s school record for receptions and tied his school record for touchdown receptions. In his final regular season game against #5 Baylor, Lockett posted 14 receptions for 158 yards and a touchdown, which gave him 27 career touchdown receptions and broke a tie with his father for the school record. With just a bowl game remaining, Lockett’s career total of 3,546 receiving yards ranked 6th in Big 12 Conference history. He added 13 receptions for 164 receiving yards and 2 touchdowns against UCLA in the January 2, 2015 Alamo Bowl. In the game, Lockett had a 41-yard punt return and had a 72-yard punt return touchdown negated due to a holding penalty. He established Alamo Bowl records for receptions (13) and all-purpose yards (249). He was recognized as the game’s Sportsmanship MVP.

He had hoped to redshirt during the 2011 season, which was his freshman year, so that he could add size. He played in 2011 as a true freshman and got off to a modest start. Lockett only recorded four receptions for 50 yards, three rushes for nine yards, one kickoff return for ten yards, and two punt returns for a total of 13 yards in his first five games through October 8. Things started to turn around on October 15 when he posted a 100-yard return of a kickoff for a touchdown against Texas Tech. Over the ensuing weeks, he earned numerous Big 12 Conference honors for the 2011 team, including becoming a two-time Big 12 Special Teams Player of the Week. His first Player of the Week recognition came on October 24 after he produced a 251-yard all-purpose yards performance on October 22 against Kansas in the Governor’s Cup that included posting a 97-yard kickoff return touchdown while becoming the first player in school history to return kickoffs for touchdowns in consecutive games and having a career-high five-reception 110-yard receiving day. His other Player of the Week recognition that season came on November 7 after a 315-yard all-purpose yard November 5 game against Oklahoma State that included an 80-yard kickoff return and three rushes for 84 yards as well as three receptions for 32 yards and a touchdown. Due to what was at first an undisclosed injury, he did not play in the final three games of Kansas State’s regular season. Later, the injury was determined to be a lacerated kidney. In the four games before the injury, he had at least three receptions and 125 all-purpose yards in each game.

Prior to the 2013 season, Lockett was recognized as a 2013 Allstate/American Football Coaches Association (AFCA) Good Works Team nominee. He opened the season with 7 receptions for 113 yards, including a 56-yard touchdown pass, against North Dakota State on August 30. The following week, he added 111 yards against Louisiana–Lafayette on 8 receptions. On September 21, he connected with quarterback Jake Waters for 13 receptions for 237 yards against Texas in the 2013 Big 12 Conference season opener and had an additional 96 return yards on kickoffs. 237 receiving yards is a Kansas State single-game record, surpassing Jordy Nelson’s 214 yards against Iowa State on November 3, 2007. This receiving yardage total was the 2nd highest in the first four weeks of the season behind Texas A&M wideout Mike Evans’ 297 yards. Lockett suffered a hamstring injury in the first half of the October 5 contest against Oklahoma State. He returned to the lineup on October 26, to post three touchdowns and 111 yards on 8 receptions and help Kansas State achieve its first Big 12 win of the season against West Virginia. On November 16, Lockett posted 8 receptions for 123 yards, including a 74-yard touchdown reception against TCU. One week later, Lockett caught 12 passes for 278 yards and 3 touchdowns against Oklahoma. He also returned 5 kickoffs for 162 yards. Lockett broke his own Kansas State single-game record for receiving yards and surpassed Darren Sproles for the Kansas State single-game all-purpose yards record (440). Lockett was named the Big 12 Conference Special Teams Player of the Week on November 25 upon becoming the all-time Kansas state leader in career kickoff return yards with 1,780. His 278 single-game receiving yards was fourth in Big 12 history and his 440 single-game all-purpose yards ranked second in Big 12 history and fifth in FBS history. Following the season, he was recognized as an All-Big 12 Conference first team selection as both a wide receiver and an all-purpose player. FWAA named him second team All-American at wide receiver and Sports Illustrated gave him honorable mention All-American recognition as an all-purpose player. In the December 28, 2013 Buffalo Wild Wings Bowl, Lockett had 10 receptions for 116 yards and 3 touchdowns against Michigan. Lockett’s performance marked the most receptions by any receiver in a Buffalo Wild Wings Bowl and the most receptions in a Bowl game by a Kansas State receiver.

On December 10, the Big 12 coaches selected Lockett as a repeat All Big 12 Special Teams Player of the Year and as a first team wide receiver. ESPN selected Lockett as the All-Big 12 first team all purpose player while the Associated Press named him a first team All-Big 12 wide receiver. Lockett was an all-purpose first team selection to the 2014 College Football All-America Team by ESPN, CBS Sports, Scout.com, American Football Coaches Association, and Sports Illustrated. He was a first team punt returner selection by the Football Writers Association of America. He was a second team selection by USA Today at wide receiver, Walter Camp Foundation at return specialist, and Associated Press as an all-purpose player. He earned the school’s eleventh consensus All-American recognition. Lockett was selected to play in the 2015 Senior Bowl. He was recognized as the 2014 Big 12 Football Scholar-Athlete of the Year. He was recognized as one of five First team Senior All-Americans from the 2014 Senior CLASS Award candidates. Lockett was recognized with the Jet Award.

In his first NFL appearance, Lockett returned a 103-yard kickoff for a touchdown against the Denver Broncos in Seattle’s preseason opener, marking the first touchdown of the preseason for the team. Four weeks later, in his NFL regular season debut, Lockett returned a 57-yard punt for a touchdown on his first career return, against the St. Louis Rams. He also posted 4 receptions for 34 yards in his debut. The following week, he made his first career regular season start against the Green Bay Packers. Lockett returned a 105-yard kick return in week 3 against the Chicago Bears, setting a new franchise record. His performance for the first three weeks of the season earned him recognition as NFC Special Teams Player of the Month for September 2015. Lockett was the first Seahawks rookie to win the award since Joey Galloway. Lockett posted his first career touchdown reception on Thursday Night Football against the San Francisco 49ers on October 22, 2015. On November 22 against the San Francisco 49ers, Lockett scored 2 receiving touchdowns. On December 6 against the Minnesota Vikings who were 8–3 at the time, Lockett had 7 receptions for 90 yards, both new career highs. One week later, Lockett had his first 100-yard receiving game and his second multi touchdown game with 104-yards, and a two-touchdown winning effort against the Baltimore Ravens. Lockett was named Pepsi NFL Rookie of the Week for his performance against the Ravens. On December 22, 2015, Lockett was selected to be part of the 2016 Pro Bowl. Lockett was one of only three rookies to be selected to the Pro Bowl, along with Rams running back Todd Gurley and Chiefs cornerback Marcus Peters. In the final week of the season on January 3 against the Arizona Cardinals, Lockett set up several scores by the Seahawks with long punt returns and receptions. His 139 punt return yards on 4 punt returns set a Seahawks single-game punt return yardage record and earned Lockett NFC special teams player of the week recognition for week 17. Three punt returns of at least 30 yards in the same game had not been accomplished by an NFL returner in at least 10 seasons. For his performance over the last 5 weeks of the season in which he amassed 759 all-purpose yards, he earned the NFC’s Special Teams Player of the Month for December/January, making him the second rookie to win the award twice (Tamarick Vanover, 1995). He joined Gale Sayers as the only rookie to record at least 5 receiving touchdowns, a punt return touchdown, and a kickoff return touchdown. He was the only rookie to be named to the Associated Press All-Pro 1st team. He was also voted along with teammate Thomas Rawls to be in the Pro Football Writers Association NFL All-Rookie Team (2015). Lockett was selected to the team at three positions: wide receiver, punt returner, and kickoff returner. For the 2016 Pro Bowl, Lockett was selected by Team Rice in a fantasy-style draft. At the Pro Bowl, he made one catch for 10 yards and returned one punt for 24 yards.

Lockett finished the 2016 season with 41 catches for 597 yards and a touchdown. In addition to his receiving numbers, he had 114 rushing yards including a 75-yard rushing touchdown, which was the longest Seattle run of the season. Lockett suffered a fracture to his right tibia and fibula while making a 28-yard catch in a Week 16 loss to the Arizona Cardinals. He had surgery later that night and was placed on injured reserve on December 27, 2016. Following the season, he was named to the 2016 All-Pro Second Team by the Associated Press.

On August 29, 2018, Lockett signed a three-year, $31.8 million contract extension with the Seahawks through the 2021 season. In the first three games of the season, Lockett totaled 12 receptions for 196 receiving yards. In addition, he recorded a receiving touchdown in each game. He finished the season as the Seahawks leading receiver with 57 receptions for 965 yards and 10 touchdowns, all career highs. When targeted by quarterback Russell Wilson, Wilson produced a perfect 158.3 passer rating. No other receiver has ever put up a perfect passer rating while being targeted more than 15 times in NFL history. In the Wild Card Round of the 2018–19 NFL playoffs against the Dallas Cowboys, Lockett had four catches for 120 yards in the 24–22 loss.

Lockett was named to the Pro Bowl on January 17, 2020 as an alternate.