After a strong pre-season, Luke Shuey made his AFL debut in round one of the 2010 season, against the Brisbane Lions and scored a goal with his first kick. He was nominated for the 2011 AFL Rising Star award in round two, after a 27-disposal and three-goal game against Port Adelaide.

After a career best season in 2016, Shuey was named in the initial All-Australian 40-man squad and won the John Worsfold Medal as the club best and fairest.

In September 2017, Shuey kicked a goal after the siren against Port Adelaide to win the first elimination final at Adelaide Oval. It was the first after-the-siren goal in extra time in AFL history.

Shuey won the 2018 Norm Smith Medal for his brilliant performance against Collingwood in the AFL Grand Final, recording 34 possessions and a goal. He received eleven out of twelve possible votes from the four judges. His team, the West Coast Eagles, won the premiership.

On 6 December 2019 it was announced that Luke Shuey would become the 11th captain of the West Coast Eagles.

After battling frequent hamstring injuries during his captaincy, Shuey announced on 8 August 2023 that he would retire at season’s end.

Luke Shuey is involved in the mental health charity organisation “A Stitch in Time”, founded by Greg Hire.