Philadelphia 76ers (2015–2018) On June 25, 2015, Holmes was selected with the 37th overall pick in the
2015 NBA draft by the
Philadelphia 76ers. On July 31, 2015, he signed with the 76ers after averaging 10 points and five rebounds in three
summer league games for the team. On November 9, 2015, he received his first career start, scoring a then-season-high 11 points in a loss to the
Chicago Bulls. He topped that mark on December 10, 2015, with 14 points against the
San Antonio Spurs. On December 28, 2015, he set a new season high with 18 points in a 95–91 loss to the
Utah Jazz. In July 2016, Holmes re-joined the 76ers for the
2016 NBA Summer League. In January 2017, he was assigned three times to the
Delaware 87ers of the
NBA Development League. He became a fixture in the Sixers' rotation in February 2017 following the
Nerlens Noel trade, the prolonged injury to
Joel Embiid, and Holmes outplaying fellow 2015 Sixers pick
Jahlil Okafor. On February 24, 2017, he had 12 points, 10 rebounds and five blocks to help the depleted 76ers defeat the
Washington Wizards 120–112. On March 20, 2017, he tied a career high in points with 24 and established a career best in rebounds with 14 in a 112–109 overtime loss to the
Orlando Magic. Nine days later, he set a new career high with 25 points in a 99–92 loss to the
Atlanta Hawks. On October 8, 2017, Holmes was ruled out for approximately three weeks after being diagnosed with a non-displaced fracture in the radial bone of his left wrist. On June 13, 2018, the 76ers announced they had exercised the fourth-year option on their contract with Holmes.
Phoenix Suns (2018–2019) On July 20, 2018, Holmes was traded to the
Phoenix Suns in exchange for cash considerations. On November 6, he had season highs of 13 points and 10 rebounds in a 104–82 loss to the
Brooklyn Nets. Holmes later recorded a new season high of 19 points in a 123–119 overtime loss to the
Los Angeles Clippers on December 10. Holmes also recorded a
double-double of 12 points and a new season high of 11 rebounds on March 15, 2019, during only 16 minutes of play in a 108–102 loss to the
Houston Rockets.
Sacramento Kings (2019–2023) On July 16, 2019, Holmes signed a two-year contract, worth $10 million, with the
Sacramento Kings. On August 6, 2021, Holmes re-signed with the Kings on a four-year, $55 million contract. On March 18, 2022, he was ruled out for the remainder of the season due to personal issues.
Dallas Mavericks (2023–2024) On July 6, 2023, Holmes, along with the draft rights to
Olivier-Maxence Prosper, was traded from the
Sacramento Kings to the
Dallas Mavericks.
Washington Wizards (2024–2025) On February 8, 2024, Holmes and a future first-round pick were traded to the
Washington Wizards in exchange for
Daniel Gafford. On June 29, he signed an extension with the Wizards. On July 14, 2025, Holmes was waived by the Wizards.
Panathinaikos (2025–2026) On 9 August 2025, Holmes signed with Panathinaikos of the Greek Basketball League (GBL) and the EuroLeague after Panathinaikos failed to secure Lithuanian centre
Jonas Valančiūnas, who ultimately remained in the NBA. His contract is a two‑year deal with a 1+1 structure, allowing the club and player to evaluate the partnership after the first season. Holmes is reported to be one of the highest‑paid players in Europe, earning approximately €2.7 million for the first year. He made his debut for the club in a friendly tournament Final (the annual Pavlos Giannakopoulos Tournament) vs the Adelaide 36ers, registering 14 points and 10 rebounds as Panathinaikos won 106‑89. In his fourth EuroLeague game of the 2025‑26 season, he produced perhaps his best performance for the club: 24 points and 10 rebounds in a 91–85 win over
ASVEL Basket, shooting 11 of 12 from the field and grabbing seven offensive rebounds. After only a handful of games into the 2025‑26 campaign, on 29 October 2025 Holmes was forced off in a EuroLeague home win over
Maccabi Tel Aviv B.C. with a knee injury, later diagnosed as a partial tear of the medial collateral ligament (MCL) in his right knee which will sideline him for approximately one month. On March 24, 2026, the team announced the termination of his contract. He had recently gotten into a public argument with the head coach,
Ergin Ataman following a game on March 15th where the coach publicly called Holmes out for his lack of effort. ==Career statistics==