Ruben Amorim's underperforming Red Devils head to the Groupama Stadium in Lyon for the first leg of this make-or-break clash on Thursday, knowing their season rests on progress against the French side.
Onana had lit the fuse by saying after Sunday's 0-0 Manchester derby draw against City at Old Trafford that overcoming Lyon, who sit fifth in Ligue 1, was "not going to be easy, but I think we are way better than them".
Those bullish remarks sparked a war of words on the eve of the game, with the normally understated Matic - who played for United between 2017 and 2022 - taking aim at the goalkeeper with surprising venom.
"I don't know - you know, to say that you need to have cover for something like that. Onana?" Matic said looking at the reporter, before puffing out his cheeks.
"You know, I respect everyone, but to say that then you need to give the answer.
"If you are one of the worst goalkeepers in Man United's history, you need to take care of what you are talking (about).
"If David De Gea or Peter Schmeichel or (Edwin) van der Sar said that, then I would question myself.
"But if you're one of the statistically worst goalkeepers in Man United's modern history, then he needs to show that before he says. We will see."
Matic's jaw-dropping comments were followed by a pointed post on X by Onana, alluding to the fact that United did not win a trophy in the midfielder's five seasons at Old Trafford.
Posting alongside a photo of himself kissing the FA Cup, the goalkeeper said: "I would never be disrespectful to another club. We know that tomorrow will be a difficult game against a strong opponent.
"We focus on preparing a performance to make our fans proud.
"At least I've lifted trophies with the greatest club in the world. Some can't say the same."
The tete-a-tete is sure to be a key talking point at United's pre-match press conference with head coach Amorim, who Matic played alongside at Benfica.