Cristiano Ronaldo's deflected free kick and a superb strike by Carlos Tevez on the stroke of halftime made it a comfortable afternoon at Old Trafford for United who moved three points clear of second-placed Liverpool.
United are on 83 points and have three games left to play to Liverpool's two. Four points from their matches at Wigan Athletic on Wednesday and at home to Arsenal next Saturday would mean they are uncatchable.
"It's a hard game at Wigan and I'll have to freshen up the team again," Ferguson, who started with Wayne Rooney on the bench on Sunday and substituted Ronaldo early in the second half, told Sky Sports.
Ronaldo appeared less than happy to be taken off but Ferguson said he wanted to give the Portuguese a rest after his two-goal display in the Champions League semi-final, second leg at Arsenal on Tuesday.
"Of course he wants to play all the time but I have to look at the bigger picture," said Ferguson, who hopes to have Rio Ferdinand back for the Wigan game after the central defender sat out the derby because of injury.
Any pressure Liverpool's 3-0 win at West Ham United on Saturday put on United soon disappeared as Ronaldo scored his 18th league goal of the season in the 18th minute with a free kick after Dimitar Berbatov had been fouled by Stephen Ireland.
Ronaldo did not strike the ball with his usual venom but it took a deflection and nestled into the corner past the slightly wrong-footed City keeper Shay Given.
Tevez, who was quoted in Sunday's newspapers as saying he wants to leave Old Trafford at the end of the season, was intent on showing United's fans what they might be missing next season.
The livewire Argentine was denied by the woodwork when he cut in and curled a great effort past Given but he was not to be denied again as the halftime whistle approached.
Berbatov controlled a high ball in an instant before picking out Tevez who fired an unstoppable shot past Given off the inside of the post.
United were never troubled after the break as they completed a league double over their mid-table city rivals.
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