Powell played AAU basketball for NJ Playaz under head coach Jimmy Salmon averaging over 18 points.

After the game, Seton Hall coach Kevin Willard joked about Powell's performance, saying “We’ve kept it real simple — get the ball to Myles and get out of the way... That's a special play call towards the end of the game.”[4] During the season, Powell received national attention as a part of the Wooden Award mid season watch list.

[10] Even though suffering the injury, he proceeded to play in the next game vs. #3 Michigan State and scored a game-high 37 points, though the Pirates fell 76–73.

[17] At the close of his senior season, Powell was named Big East Player of the Year and won the Jerry West Award.

He also became the Pirates' first consensus first-team All-American since 1953 (Walter Dukes) and became the first player in school history to win the Haggerty Award twice.

[28] Powell, who was a childhood supporter of the Philadelphia 76ers and Allen Iverson, described "having cried for the first 45 minutes" after he realized he would join the Sixers.

[29] On July 27, 2022, Powell signed a contract with the Bay Area Dragons of the East Asia Super League.

[32] In the summer of 2019, Powell was a part of the United States National team who competed at the Pan American Games in Peru.

On November 14, 2017, Noel Powell III was involved in a murder at an Applebee's restaurant in Lawrenceville, New Jersey, for which he was sentenced to seven years in prison in 2021.

Filed in the New Jersey Superior Court, the lawsuit claimed Seton Hall University, its men's basketball coach, Kevin Willard, and its Director of Sports Medicine, Tony Testa, acted negligently by letting Powell play on a torn meniscus in his right knee, which he had been told was only a minor injury that would not be further injured if he continued to play during the 2019–20 season.