He played college basketball for the Syracuse Orange and was selected with the fourth overall pick in the 2012 NBA draft by the Cleveland Cavaliers.

Waiters also played for the Oklahoma City Thunder, Miami Heat, and the Los Angeles Lakers, where his team won an NBA championship.

[3] Waiters committed to Syracuse during the summer after his freshman year despite not having played a minute of high school basketball.

Many scouts also found it a surprise that Waiters was drafted so high because he did not start in college and played zone defense at Syracuse.

[8] Waiters was selected to play in the Rising Stars Challenge game during 2013 NBA All-Star Weekend, along with teammates Kyrie Irving, Tristan Thompson, and Tyler Zeller.

He was consistently bothered by a sprained ankle and loose cartilage in his knee, forcing him to miss 21 games over the year.

On March 18, 2014, Waiters recorded his first career double-double with 17 points and a career-high 11 assists in a loss to the Miami Heat.

[12] On November 5, 2014, Waiters was absent for the U.S. national anthem and was quoted saying that he stayed in the locker room because of his Muslim faith.

[16] On April 15, 2015, in the team's final game of the season, Waiters tied his career-high with 33 points in a 138–113 win over the Minnesota Timberwolves.

[18] With a knee injury to Roberson in late January, Donovan entrusted Waiters with stepping up to a starting role.

[21] In Game 2 of the Thunder's semi-final series against the San Antonio Spurs, with San Antonio trailing 98–97 with 13.5 seconds remaining and Oklahoma City out of timeouts, Waiters elbowed Spurs guard Manu Ginóbili to get the space needed to inbound the ball.

[31] Two days later, he made a three-pointer with 0.6 seconds left to cap his second-straight 33-point effort, as he lifted the Heat to a 105–102 win over the Golden State Warriors.

[38] On December 28, 2018, Waiters was sent to Miami's NBA G League affiliate team, the Sioux Falls Skyforce, for a rehabilitation assignment.

[42] On October 19, 2019, Waiters was suspended for Miami's 2019–20 season debut game for "conduct detrimental to the team.

[45] On December 12, the Heat suspended him again, this time for six games, for calling in to work with an illness, then posting a picture of himself on his Instagram page on a boat celebrating his birthday.

[46][47] On January 24, 2020, Waiters made his season debut scoring 14 points in a 122–117 loss against the Los Angeles Clippers.

On July 13, 2023, he held a private workout in front of NBA scouts at the Victoria Fertitta Middle School, for a chance to re-join the league.