After the season, Looney decided to forgo his college eligibility and enter the 2015 NBA draft, and was selected in the first round by Golden State with the 30th overall pick.

In his only season at UCLA, Looney led all freshmen in the nation in double-doubles, recording double figures in both points and rebounds in 15 games.

[2] Growing up, he was coached by his father, who played as a forward at Schreiner University in Kerrville, Texas, and became the school's career rebounding leader.

[2][7] As a junior, he averaged 26.1 points, 12.4 rebounds, 7.0 blocks, and 3.1 assists per game, leading a team of mostly unproven players to a runner-up finish for the conference title.

[4][11] Capable of handling the ball, creating his own shot, and shooting,[12] mixtapes on YouTube hailed Looney as "the next KD", in reference to future Golden State teammate Kevin Durant.

[a][21] Soon, pundits began projecting Looney as a freshman lottery pick should he decide to enter the National Basketball Association (NBA).

[9][24][25] Looney had seven double-doubles in the Bruins' first 10 games, before scoring in double digits just once during a five-game losing streak for UCLA, which included an 0–2 start to their Pac-12 Conference schedule.

[27][28] He was one of 14 players named to the United States Basketball Writers Association (USBWA)'s mid-season watchlist for the Wayman Tisdale Award, presented annually to the nation's top freshman.

[43] One of 19 players to attend the draft, Looney fell to the final pick of the first round, where he was chosen 30th overall by the Golden State Warriors.

[41][45][46] On July 8, 2015, Looney signed his rookie scale contract with the Warriors,[47] and played on their Las Vegas Summer League team.

[48] On January 4, 2016, Looney was assigned to the Santa Cruz Warriors, Golden State's D-League affiliate, after being cleared to practice after rehab from his surgery.

[49][50] Looney made his professional debut on January 12 with Santa Cruz, logging a double-double with 11 points and 12 rebounds in 16 minutes against the Idaho Stampede.

On April 22, Looney underwent a successful arthroscopic surgery to repair a torn labrum on his left hip, which was expected to sideline him from four to six months.

[63] On November 26, 2016, he made his first career start in place of an injured Draymond Green, recording six points, three rebounds, and two assists in 18 minutes of play in a 115–102 victory over the Minnesota Timberwolves.

He lost 30 pounds (14 kg) before the season after hiring a personal trainer over the summer, changing his training program, and adopting a modified Paleo diet.

[61][68] However, Looney was one of six centers on the team, behind starter Zaza Pachulia and veterans David West and JaVale McGee, while youngsters Jordan Bell and Damian Jones appeared to have brighter futures.

Finally able to play extended minutes without being out of breath, he helped lead an 18-point second-half comeback after Green was ejected late in the second quarter.

[61][70] On October 31, Golden State did not exercise its fourth-year option on Looney for 2018–19 due to his contract's luxury tax impact on their payroll, making him an unrestricted free agent the following summer.

"[72] On November 11, in a 135–114 win over the Philadelphia 76ers, Looney had four points and three blocked shots with a plus–minus of +14 in 15 minutes while matched up mostly opposite Joel Embiid, one of the league's top centers.

He played the final 6:30 of the game and was more effectively switching defensively on Rockets guard Chris Paul than Bell, who remained on the bench in the second half.

"[77] On January 12, Looney returned to his hometown and played a career-high 23 minutes while scoring nine points on a perfect 3-of-3 shooting with another eight rebounds, three assists and a block in a 108–94 victory over the Milwaukee Bucks.

[84] In the final two games, Looney became the Warriors' sixth man after the team went small and started their Hamptons Five lineup with Green at center.

[92] Golden State also added four-time NBA All-Star center DeMarcus Cousins with their mid-level exception, but he was rehabbing his left Achilles tendon and had no definitive timeline on returning.

[99] Looney ended the regular season averaging career highs in points (6.3), shooting percentage (62.5 percent), rebounds (5.2) and minutes played (18.5).

[100] In Game 2 of the Warriors' first-round playoff series against the Los Angeles Clippers, following a first-quarter injury to Cousins, Looney scored a career-high 19 points during a 135–131 loss.

[101] With Cousins expected to be out for the remainder of the playoffs, Kerr started Andrew Bogut—the former Warrior who was acquired late in the season—to keep Looney in the backup role where he had excelled.

[115] Looney was sidelined following the 2019–20 season-opener after tightness in his hamstring was diagnosed as neuropathy,[116] a disorder resulting from nerve damage outside of the brain and spinal cord.

[132] In Game 5, Looney had 10 points and 18 rebounds, including seven on the offensive end, helping the Warriors win the series 4–1 and advance to their sixth NBA Finals in eight years.

[134] Looney won his third championship, averaging 7.5 rebounds and 5.0 points as the Warriors defeated the Boston Celtics in six games in the 2022 NBA Finals.

He became the first NBA player with three games of 20 or more rebounds in a series since Dwight Howard in 2008, and joined Wilt Chamberlain and Nate Thurmond as the third Warrior to accomplish the feat.