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Nigeria coming from behind to secure a point against Equatorial Guinea in just the second match of the finals only hinted at the upsets to come.
Record seven-time champions Egypt took the lead after 89 seconds against lowly Mozambique, but needed a 97th-minute penalty from Mohamed Salah to scrape a 2-2 draw, setting the tone for the thrills to come.
Former winners Ghana, Algeria and Tunisia all failed to progress to the last 16, with Equatorial Guinea, Cape Verde and Angola all finishing top of their respective groups.
Ivory Coast suffered an astonishing 4-0 defeat by the Equatoguineans in their final Group A match, watched by their iconic striker and two-time finalist Didier Drogba.
The West Africans matched their unenviable record of being the only host nation to lose two group games, having been the first to do so when they laid on the tournament in 1984.
Arguably the shock of the group stage came courtesy of Namibia, with the side ranked 115th in the world earning their first win at the finals at the 10th attempt by beating 2004 champions Tunisia 1-0.
That triumph helped the Brave Warriors to progress, while there were unforgettable moments even when the odds were not overturned.
On the same night that Mauritania beat Algeria to condemn the 2019 champions to a second successive exit at the first hurdle, The Gambia and Cameroon took part in an extraordinary Group C settler.
The Indomitable Lions, five-time Afcon winners, were on their way out when the lowest-ranked team at the tournament took an 85th-minute lead, but two late goals saw the Central Africans progress.
Defending champions Senegal, meanwhile, eased through to the last 16 serenely as the only side with a 100% record.