He was selected with the seventh overall pick in the 2011 NBA draft by the Sacramento Kings and subsequently traded to the Charlotte Bobcats (now Hornets).

Biyombo has also played for the Toronto Raptors, Orlando Magic, Phoenix Suns, Memphis Grizzlies, and Oklahoma City Thunder.

He started the 2010–11 season with CB Illescas before moving to Baloncesto Fuenlabrada of the first-tier Liga ACB in January 2011.

[3][1] Biyombo made his debut at age 18 in the Spanish ACB League with Fuenlabrada against DKV Joventut on January 9, 2011, recording 5 points and 7 rebounds in just over 13 minutes of play.

[10] On June 30, 2015, the Hornets decided not to extend a qualifying offer to Biyombo, making him an unrestricted free agent.

[14] He made his debut for the Raptors in the team's season opener against the Indiana Pacers on October 28, recording 7 points and 5 rebounds in a 106–99 win.

[15] Biyombo started in 18 straight games between mid-November and late December while Jonas Valančiūnas was recovering from a fractured hand.

On March 17, 2016, Biyombo scored a career-high 16 points and set a franchise record with 25 rebounds in guiding the Raptors to a 101–94 overtime win over the Indiana Pacers.

[27][28] After exceeding the flagrant foul limit during the 2016 playoffs, Biyombo was forced to serve an NBA-mandated one-game suspension to begin the 2016–17 season.

[29] He made his debut for the Magic in the team's second game of the season on October 28, scoring two points in just under 23 minutes in a 108–82 loss to the Detroit Pistons.

[52] On March 6, Biyombo unexpectedly collapsed to the floor on his team's sideline during a game against the Portland Trail Blazers.

[55] He enjoys reading in his spare time and speaks five languages: English, French, Lingala, Spanish and Swahili.

[57] After fainting during an NBA game in 2024 due to dehydration, Biyombo revealed that he has been fasting regularly for 13 seasons as a personal devotion to his Catholic faith.

During the COVID-19 pandemic in 2020, the foundation donated around $1 million worth of medical supplies to people in the Democratic Republic of the Congo.

[58] In March 2022, Biyombo announced that he had pledged his salary from the entire 2021–22 season towards the construction of a hospital in Congo, in honor of his father.