The Bees striker had given the visitors the lead in the 16th minute before Phil Foden levelled on the stroke of half-time with a stunning equaliser.
City pushed for a winner with Joao Cancelo and Rodri forcing saves from David Raya but they were caught on the break deep in injury time when Toney swept in a late winner.
It brought an end to a run of 15 consecutive home victories in all competitions and means we will go into a break for the World Cup second in the Barclays Premier League.
Brentford have not won away in the Premier League all season but showed no fear at the home of the champions and inside three minutes, Frank Onyeka forced an early sprawling save from Ederson.
Toney in particular looked like he had an extra point to prove after being omitted from Gareth Southgate’s England squad in midweek and he was denied by another superb Ederson save from close range shortly after.
And he put the Bees ahead in the 16th minute when he reacted to Ben Mee’s flick-on to loop a header just over Ederson and under the crossbar.
City had a big shout for a penalty 10 minutes later when Rico Henry handled the ball as Bernardo Silva broke into the box, but after a VAR check, contact was adjudged to have been narrowly outside the area.
Brentford survived the resulting free-kick but City finally got the equaliser just before half-time.
There was a five-minute stoppage at the start of the second half when Aymeric Laporte suffered a nasty gash to his head in an accidental collision but he was able to carry on and stopped Brentford snatching a goal on the break with a last-ditch clearance as Toney threated to turn in Henry’s cross.
City pinned back the visitors for much of the second half but clear opportunities were difficult to create.
Rodri and Cancelo both forced good saves from Raya with long-range efforts while Foden also tried his luck from a distance with a sharp turn and strike over the bar.
With 10 minutes of injury time, City searched for a second successive Premier League victory after the 90th minute.
But it was Toney who grabbed a late winner and almost snared a hat-trick as City pushed forward with Ederson making another smothering save.
What it means
City will stay second going into the break for the World Cup behind leaders Arsenal who can extend their advantage with a win at Wolves at 19:45pm.
We now have a break as the bulk of our squad head off to the World Cup in Qatar.
Our next game is scheduled for the week beginning 19 December against Liverpool at the Etihad in the fourth round of the Carabao Cup.
The date and kick off time is to be confirmed and mancity.com will have the details as soon as it is confirmed.
BRENTFORD: Raya, Roerslev, Mee, Pinnock, Henry, Jensen, Janelt (Norgaard 62), Jorgensen, Onyeka (Dasilva 87), Mbeumo (Wissa 74), Toney.
Subs: Cox, Canos, Ghoddos, Lewis-Potter, Crama, Yarmoliuk.
STATS, FACTS AND MILESTONES
- City have never won three consecutive league games against Brentford in 11 games.
- Brentford’s win was their first away at City since Christmas Day in 1937.
3 - Ivan Toney has scored 2+ goals on three occasions in the Premier League this season; only Erling Haaland (5) has done so in more different matches.— OptaJoe (@OptaJoe) November 12, 2022
3 v Leeds United
2 v Brighton
2 v Manchester City
"The better team won," he said in his post-match press conference.
"We had a lot of problems and we could not press as they didn’t allow us. In this process when they gave it to the striker we could not do it.
"When Toney flicked the ball on while playing through the middle he created problems."
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