Images shared on social media, which Reuters could not immediately authenticate, showed a panicked crowd trying to squeeze through a narrow entrance gate at the newly built Olembe stadium in Yaounde that was hosting a round of 16 games between Cameroon and Comoros.
One video showed dozens of fans scrambling over the stadium fence as a police officer walked by.
The stampede comes as a heavy blow for the tournament, which had grown in excitement on the pitch in recent days thanks to some match upsets but which was under scrutiny for a lack of readiness beforehand.
COVID-19 and insecurity caused by a separatist insurgency also complicated preparations.
Work on the 60,000-seat Olembe Stadium continued right up to the start of Africa's top soccer tournament, prompting the Confederation of African Football (CAF), the continent's soccer governing body, to hold an emergency meeting to discuss cancelling the competition altogether.
"CAF is currently investigating the situation and trying to get more details on what transpired. We are in constant communication with Cameroon government and the Local Organising Committee," it said in a statement.
THE SHOCK, THE WEIGHT
High school teacher Vanessa Tchouanzi had come to see the match on Monday. She was barely able to get her words out as she recounted her experience over the phone to Reuters.
Tchouanzi tried to enter the stadium with a friend but said that gate attendees were too overwhelmed by the mass of people to check tickets.
As fans rushed the entrance, Tchouanzi and her friend were knocked to the ground. A bystander helped Tchouanzi escape, but her friend was trampled to death, she said.
"She couldn't take the shock, the weight of all those people," Tchouanzi said through a flood of tears.
The government did not give any information on the cause of the crush or whether fans were allowed into the stadium without tickets. It is not clear why the match went ahead after the disaster.
Following a low turnout in the first round games at brand new stadiums, Cameroon authorities have thrown open stadium gates, organised mass transport and given out free tickets to lure fans.
Cameroon beat 10-man Comoros Islands 2-1 to advance to the quarter-finals.