Holmes agreed to a five-year contract to join Detroit, sources told NFL Network's Ian Rapoport. He replaces Bob Quinn, who spent the last five years in the role and was fired in November.
The executive becomes the third person of color who currently holds a GM position in the NFL, joining Chris Grier of the Miami Dolphins and Andrew Berry of the Cleveland Browns.
"When we embarked on this process, it was critical that we find the right person to fit our vision for this team," Lions owner Sheila Ford Hamp said in a statement. "It was evident early on that Brad is a proven leader who is ready for this opportunity."
Los Angeles will be the first team to receive two third-round compensatory draft picks as part of the league's new hiring initiatives, according to ESPN's Adam Schefter.
Holmes was one of at least 12 candidates the Lions interviewed for their opening. He was reportedly also a finalist for the Atlanta Falcons' position, Rapoport notes.
As director of college scouting with the Rams, the 41-year-old played a major role in the club's last eight drafts, which featured the selections of Aaron Donald, Jared Goff, Todd Gurley, and Cooper Kupp.
Holmes will now be involved in the Lions' search for a new head coach.