Brooklyn Nets (2015–2019) On June 25, 2015, Hollis-Jefferson was selected by the
Portland Trail Blazers with the 23rd overall pick in the
2015 NBA draft. His draft rights, along with
Steve Blake, were subsequently traded to the
Brooklyn Nets for
Mason Plumlee and the draft rights to the 41st overall pick,
Pat Connaughton. On July 6, 2015, he signed his rookie-scale contract with the Nets. He made his debut for the Nets in their season opener on October 28, 2015, recording eight points and five rebounds off the bench in a 115–100 loss to the
Chicago Bulls. On November 20, he had a season-best game with 13 points and 11 rebounds as a starter in a loss to the
Boston Celtics. On December 7, he was diagnosed with a non-displaced fracture of the posterior talus in his right ankle, an injury requiring surgery and eight to ten weeks of rehabilitation. He returned to action in late March. On November 12, 2016, Hollis-Jefferson scored a then career-high 20 points and tied a career high with 13 rebounds in a 122–104 win over the
Phoenix Suns. On December 14, 2017, Hollis-Jefferson scored a career-high 25 points on 10-for-16 shooting in a 111–104 loss to the
New York Knicks. He strained his right groin during a 116–91 loss to the
Milwaukee Bucks on January 26, returning to action on February 26 against the Chicago Bulls after missing the Nets' previous 11 games. Hollis-Jefferson missed the first three games of the 2018–19 season with a hip injury and the birth of his first child. On November 28, 2018, in a 101–91 loss to the
Utah Jazz, Hollis-Jefferson had 14 points and a season-high 11 rebounds for his first double-double. On March 19, 2019, he made a layup with eight-tenths of a second remaining to lift the Nets to a 123–121 win over the
Sacramento Kings. On June 17, the Nets opted not to make Hollis-Jefferson a qualifying offer, making him an unrestricted free agent.
Toronto Raptors (2019–2020) On July 18, 2019, Hollis-Jefferson signed with the defending champion,
Toronto Raptors. On December 3, 2020, Hollis-Jefferson signed a non-guaranteed preseason contract with the
Minnesota Timberwolves. He was waived by the Timberwolves shortly after he signed on December 19, 2020.
Portland Trail Blazers (2021) On April 8, 2021, Hollis-Jefferson signed a 10-day contract with the
Portland Trail Blazers. On April 18, he signed a second 10-day contract and 10 days later, he signed for the rest of the season after appearing in six games.
Beşiktaş (2021–2022) On September 28, 2021, Hollis-Jefferson signed with
Beşiktaş Icrypex of the
Basketbol Süper Ligi. He scored a career-high 26 points in a 69–82 loss over the Rytas.
Atléticos de San Germán (2022) On April 11, 2022, Hollis-Jefferson signed with
Atléticos de San Germán of the
Baloncesto Superior Nacional. He played 31 games and averaged 19.7 points per game. On May 16, 2023, Hollis-Jefferson was brought back by Atléticos de San Germán. He played 22 games and averaged 21.7 points per game.
TNT Tropang Giga (2023–2024) In February 2023, Hollis-Jefferson signed with the
TNT Tropang Giga of the
Philippine Basketball Association (PBA) to replace
Jalen Hudson as the team's import for the
2023 PBA Governors' Cup. He played 16 games and averaged 30.4 points per game. On May 30, 2023, it was announced that Hollis-Jefferson will return as the team's import for the
2023–24 PBA Commissioner's Cup.
Mets de Guaynabo (2024) On February 12, 2024, Hollis-Jefferson joined the
Mets de Guaynabo after a trade with San Germán.
TNT Tropang Giga (2024–present) In August 2024, Hollis-Jefferson returns to TNT as the team's import for the
2024 PBA Governors' Cup. He helped the team clinch their second consecutive Governors' Cup title, scoring 31 points in a series-clinching 95–85 victory against the
Barangay Ginebra San Miguel in Game 6 of the
Governors' Cup finals. After the championship in Governos' Cup, Hollis-Jefferson helped TNT captured the Commissioner's Cup against Barangay Ginebra in Finals Game 7, giving TNT a back-to-back championships in one season. Hollis-Jefferson received His 3rd Best Import of the Conference award. In April 2025, Hollis-Jefferson signed 1-year "exclusive" contract for the TNT. In September 2025, TNT allowed Hollis-Jefferson to play for its sister-team
Meralco Bolts for their campaign on
East Asia Super League.
Meralco Bolts (2025) On September 11, 2025, Hollis-Jefferson joined the
Meralco Bolts of the
East Asia Super League as an import. In a December 6 game against the
Macau Black Bears, Hollis-Jefferson suffered a
ruptured Achilles tendon, ending his season. ==Philanthropy and community work==