Lokombo was born in Kinshasa, Zaire, but moved to Montreal, Quebec in 1996. Lokombo was raised in Abbotsford, British Columbia, where he attended W. J. Mouat Secondary School. As a senior, he recorded 47 tackles with four interceptions and also played wide receiver and running back. He ran for 1,556 yards on 107 carries and 22 touchdowns, and caught 37 passes for 728 yards. He was named the Provincial AAA Eastern Conference All-Star Offensive MVP. He played his junior prep season at South Eugene High School in Eugene, Oregon where he recorded more than 50 tackles. Considered a three-star recruit by Rivals.com, he was rated as the 27th best outside linebacker prospect of his class.
In the Canadian Football League's Amateur Scouting Bureau final rankings, he was ranked as the best player for players eligible in the 2013 CFL Draft. Because he was a probable National Football League draft selection in 2014, his CFL draft stock fell, leading him to be drafted in the third round, 21st overall, by his hometown BC Lions. He returned to play with the Oregon Ducks for the 2013 season, but went undrafted and unsigned in the NFL. He signed with the BC Lions on September 8, 2014. Joining the Lions midway through the season Lokombo spent one game on the injured list before being activated to the Lions' 46-man roster and appearing in the final seven regular season game as well as the post-season. Seeing action exclusively on special teams, he recorded nine tackles on the year, good enough for seventh place on the club. In 2015 Lokombo saw action mostly on special teams. He recorded 26 defensive tackles, good for 12th on the team, despite limited action. He got his first CFL sack on a missed snap in a game at Hamilton. Bo Lokombo excelled on special teams leading the league with 24 tackles, earning his first CFL West All-star. The Lions granted early free agent status to Lokombo so he could pursue an NFL opportunity.
Baltimore Ravens
On January 31, 2017, Lokombo signed a reserve/future contract with the Baltimore Ravens. He was waived on September 2, 2017 and was signed to the Ravens' practice squad the next day. He was released on September 26, 2017.
Oakland Raiders
On September 28, 2017, Lokombo was signed to the Oakland Raiders' practice squad. He was released on October 10, 2017.
On November 29, 2017, Lokombo was signed to the San Francisco 49ers' practice squad. He signed a reserve/future contract with the 49ers on January 2, 2018. Lokombo was released on April 30, 2018.
BC Lions (II)
On May 7, 2018 the BC Lions announced that Boseko Lokombo would be returning to the CFL, having signed a new contract to play for the Lions. He recorded 71 defensive tackles, 16 special teams tackles, four sacks, and two interceptions in 18 regular season games.
On the first day of 2019 free agency, Lokombo signed a one-year contract with the Montreal Alouettes. He played in 15 regular season games where he had 51 defensive tackles, 8 special teams tackles, and two interceptions as he split time between linebacker and safety.
Toronto Argonauts
As a pending free agent, Lokombo's playing rights were traded to the Toronto Argonauts on January 31, 2020.
