The 30-year-old was guarding the posts for just eight minutes at St James' Park, having come off worse in a collision with Sean Longstaff during the earliest exchanges of the match.
Ederson required treatment after the clash with Longstaff - which was an avoidable incident due to the offside flag going up late as per the rules - and he initially tried to soldier on.
However, the Brazil international dropped to the turf again only a few moments later, and Guardiola immediately signalled for a substitution, bringing on Stefan Ortega to see out the remaining 82 minutes.
Ederson was captured limping up the stairs in the tunnel after being taken off, sparking fears about a potentially serious knee problem, but with his injury being a contact rather than non-contact issue, Guardiola is hopeful that it will not prove to be severe.
"He had a big knock. I didn't speak with the doctors. He didn't walk well as he left the pitch but if it is just a knock he will be fine because we have a break for 10 days. If there is some damage, the doctors will tell me," the Manchester Evening News quotes Guardiola as saying.
So far this season, Ederson has only missed one Premier League match for the champions - sitting out their 2-1 win over Brighton & Hove Albion on October 21 due to his late arrival back from international duty in South America.
In terms of injury-related absences, though, Ederson has not been forced to sit out a Citizens fixture since November 2019, and he was last absent through COVID-19 in January 2021.
The 30-year-old has once again been a crucial performer for Guardiola in the 2023-24 campaign, keeping nine clean sheets in 26 games across four separate tournaments for the treble winners.
However, Ederson would not be expected to start City's next fixture injured or not, as the Citizens continue the defence of their FA Cup title away to Tottenham Hotspur on January 26 in the fourth round.
During City's run to FA Cup glory last season, Ederson's only appearance came in a 3-0 fifth-round win over Bristol City, with Guardiola putting his faith in Ortega for the rest of the competition.
Having also given Ortega the nod for their third-round beating of Huddersfield Town, Guardiola would be expected to stick with the German against Spurs, after which Ederson could make his comeback against Burnley on January 31 in the Premier League.
Following Ederson's enforced withdrawal, Man City drew first blood at St James' Park through Bernardo Silva's smart flick before a quickfire brace from Anthony Gordon and Alexander Isak turned the game on its head.
However, the returning Kevin De Bruyne inspired a stunning second-half turnaround, netting the visitors' equaliser in the 74th minute before teeing up Oscar Bobb for an injury-time winner to move the champions up to second in the table.
Guardiola's side now have just a two-point disadvantage to make up to leaders Liverpool, while Aston Villa are level on points with the champions in the table having played a game more.