Forest star Morgan Gibbs-White took a shot from the edge of the box that appeared to be heading straight towards Onana.
It looked like it would be a regulation save for the United gloveman.
However, Onana had already fallen towards the right and could only watch as the ball rolled past his outstretched left leg.
talkSPORT commentators Jason Cundy and Jamie O'Hara couldn't believe the calamity they'd just witnessed.
"What is he doing?" Cundy said. "It's disgusting!"
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"There's no deflection. What's going on?"
O'Hara added: "One of the worst saves I've ever seen. What's he doing? Centre of the goal, that's embarrassing!
"If that went in in an under-eight game, and the keeper let that in, you'd go, 'What are you doing?' It's straight at him and he dives out of the way!"
Cundy said: "It's like he's tripped over. He's got that in his DNA, doesn't he?"
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Gibbs-White's goal was not the first time Onana has been made to look foolish against Forest.
In August last season, Onana tried to pre-empt which way Forest forward Taiwo Awoniyi would shoot as he raced towards goal, only to fall on his backside.
It left Awoniyi with almost the entire goal to aim at and he did not miss.
Gibbs-White's goal put Nottingham Forest 2-1 up against Man United following Nikola Milenkovic's opener just two minutes in.
Rasmus Hojlund drew the game level shortly after, however Gibbs-White's 47th-miute strike put Forest in control.
Things then went from bad to worse when Chris Wood made it 3-1 to Forest, leaving Old Trafford shell-shocked.
Wood's goal also ensured he had a slice of club history as he became Forest's all-time Premier League goalscorer with 25 to his name.
However, United skipper Bruno Fernandes sparked hopes of a comeback when he reduced the deficit to 3-2 just seven minutes after.
Fernandes capped off a rapid counter-attack as he swept home a pass inside by the box from Amad Diallo, who has impressed as a right wing-back in Red Devils boss Ruben Amorim's system.
Despite the home side's best efforts, a third goal was not forthcoming as Forest recorded their first win at Old Trafford in 30 years.
The result also marked only the second time in Amorim's managerial career he has lost back-to-back league games.
Forest's win lifted them up to fifth in the table and are just two points behind defending Premier League champions Manchester City.
As for United, the defeat kept them in 13th on 19 points.