After a third-quarter possession, Cunningham visited Louisville's medical tent following a hit to the head. He came back for two full series before walking off on his own power alongside a team trainer.
"Malik just couldn't go back in. He just got an undisclosed injury and couldn't go back in," Cardinals coach Scott Satterfield said. "We're gonna have to evaluate him when we go back to Louisville. We'll see where he's at, and what the status will be on Sunday or Monday."
Backup Brock Domann replaced Cunningham in the fourth quarter but struggled, finishing 1-of-7 for 19 yards as the Cardinals (2-3) fell to 0-3 in the ACC.
"We gotta do a better job of getting free and getting open from those guys, including the last drive when Malik wasn't in there," Satterfield said.
Cunningham was his usual self against the Eagles (2-3, 1-2) before the injury. He completed 19 of 28 passes for 186 yards and a touchdown and ran for 52 yards and three scores on 14 carries. He passed Baltimore Ravens quarterback Lamar Jackson for fourth on the school's passing yardage list.
Ranked No. 21 in ESPN's top 50 NFL draft prospects by position, Cunningham had 782 passing yards and 395 rushing yards headed into the league game, accounting for eight total touchdowns. Last season, he threw for 2,941 yards and 19 scores.
The Eagles were shorthanded on offense, as well. Starting left guard Finn Dirstine was ruled out just prior to kickoff with an upper-body injury. Boston College was down three players who were expected starters on the offensive line this summer.
The Eagles were efficient on offense, however, securing their first win over an FBS team this season. Phil Jurkovec threw for 304 yards and three touchdowns and scrambled for a 33-yard run that set up the game-winning field goal.
The Associated Press contributed to this report.