The 24-year-old was substituted just 21 minutes into Belgium's 4-1 win over the United States in the last 16 in Seattle, going down clutching his knee after a challenge with Christian Pulisic. He was treated on the pitch before limping off, and was later pictured on crutches wearing a knee brace.
Belgium team doctor Brahim Hacene confirmed the extent of the damage in a statement.
"Unfortunately, the medical examinations have confirmed that Amadou has suffered a rupture of the anterior cruciate ligament," he said. "We immediately consulted with Amadou and with Aston Villa to agree on the best approach to his recovery.
"Over the coming days, we will jointly determine the next steps in his medical treatment and rehabilitation. We will continue to provide Amadou with our full support."
Belgium confirmed Onana would remain with the squad for their quarter-final against Spain in Los Angeles on Friday, despite playing no further part in the tournament. Partial tears or ruptures of the ACL typically rule players out for between six and nine months, meaning Onana faces a race to be fit for a significant chunk of the season ahead.
Onana started Belgium's opening game of the tournament, a 1-1 draw with Egypt, before coming off the bench in wins over New Zealand and Senegal. Belgium head coach Rudi Garcia had already sounded the alarm after the win over the USA, saying he feared his midfielder had picked up a serious injury and that the mood in the camp was far from celebratory despite reaching the last eight for the first time since finishing third at the 2018 World Cup in Russia.
The injury is a significant blow for Villa as well as Belgium, with Onana having been earmarked as a central figure in Emery's plans for a season that will include Champions League football after Villa won the Europa League and finished fourth in the Premier League last term.
The Belgian joined Villa from Everton for £50million in July 2024 and made 38 appearances last season, scoring twice, and Villa are now expected to explore the transfer market for cover in his position.