Having finished the opening day's running around the unique street circuit three tenths of a second off a flying Ferrari's pace, Mercedes' apparent work overnight to improve their W17's set-up paid immediate dividends on the return to the track.
Antonelli, chasing a fifth successive victory this weekend to extend a 43-point title lead, set an impressive time of 1:12.720 to outpace Ferrari's Charles Leclerc by 0.327s.
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Leclerc's first lap on his qualifying simulation, which would normally have been his quickest, was badly compromised by traffic in the final sector, but the Monegasque was already 0.2s down on Antonelli by the end of sector two. Leclerc also again struggled with his car's brakes.
"Mercedes have turned things around," said Sky Sports F1's Anthony Davidson.
"Really impressive stuff from Antonelli too."
Friday pacesetter Lewis Hamilton was 0.004s behind team-mate Leclerc in third, with George Russell fourth in the second Mercedes after his soft-tyre run did not go entirely to plan, and he wound up 0.7s behind Antonelli.
Max Verstappen had been Ferrari's closest challenger on Friday but Red Bull struggled to stay with the leaders as the pace upped in final practice, the Dutchman finishing 0.9s off Antonelli's pace and now looking far less like a pole contender.
McLaren remain the best part of a second off the pace and appear set to qualify on the third row at best with Oscar Piastri sixth and Lando Norris, whose car was fixed overnight after it stopped due to technical issues in P2, ninth.
An impressive Audi still lead the midfield with Gabriel Bortoleto in seventh and Nico Hulkenberg in 10th continuing to run around the off-colour McLarens and the second Red Bull of Isack Hadjar, who was eighth.
Oliver Bearman caused a red flag in the closing 15 minutes when he crashed into the barriers after getting out of shape at the top of the hill into Massenet.
Bearman, who finished 14th fastest, quickly apologised to his team over the radio.
"Sorry guys. It's the bottoming! Oh my gosh," he said, with his Haas mechanics now in a race against time to repair his car for qualifying at 3pm.
Franco Colapinto had earlier damaged his Alpine when he spun and tagged the barriers at the slower-speed hairpin.
Sky Sports F1's Monaco GP live schedule
Saturday June 6
1.10pm: F2 Sprint
2.15pm: Monaco GP Qualifying build-up
3pm: MONACO GP QUALIFYING*
Sunday June 7
6.50am: F3 Feature Race
8.30am: F2 Feature Race
10.50am: Porsche Supercup
12.30pm: Monaco GP build-up: Grand Prix Sunday*
2pm: THE MONACO GRAND PRIX*
4pm: Monaco GP reaction: Chequered Flag*
*Also on Sky Sports Main Event
Watch the Monaco Grand Prix, the first of six races in eight weeks, live on Sky Sports F1 this weekend. Stream Sky Sports with NOW - no contract, cancel anytime
