Webb was famously mocked-up in a red United shirt on Twitter by Liverpool's Ryan Babel amid huge criticism for his performance in United's FA Cup victory over the Merseysiders in January.
Mock-up: Ryan Babel posted this photoshopped image of Howard Webb on Twitter
Babel, who left Anfield later that month, was subsequently fined ?10,000 by the Football Association over the incident.
Sunday's clash at Old Trafford could well decide who wins the Barclays Premier League later this month.
United's defeat at Arsenal at the weekend leaves them just three points ahead of Chelsea, who are in a fine run of form in the league. Victory for the Blues would propel them to the top of the table on goal difference with just two games of the season remaining.
Up in arms? Sir Alex Ferguson takes charge of United training on Tuesday morning
The appointment of World Cup final referee Webb was confirmed on Tuesday afternoon by Mike Riley, the head of the Professional Game Match Officials (PGMOL) body, which selects officials.
The appointment is crucial and not just because of the importance of the match. It comes after another controversial weekend in the Premier League that included Frank Lampard's goal against Tottenham that replays showed did not cross the line.
United manager Sir Alex Ferguson has stoked up the build-up to the game by suggesting that Chelsea had been the beneficiary of some 'great decisions' in their 2-1 win over Tottenham at Stamford Bridge.
Title duel: Chelsea and Manchester United will go head-to-head at Old Trafford
Meanwhile, the FA will study Ferguson's comments about referee Chris Foy at Arsenal but are unlikely to take further action.
Ferguson has only recently returned to the touchline after a five-game ban and ?30,000 fine imposed for criticising match officials.
He hit out at Foy for not awarding a late penalty for Gael Clichy's challenge on Michael Owen as United's 1-0 defeat at the Emirates.
Comments: Sir Alex Ferguson criticised Chris Foy after Sunday's defeat at Arsenal
'It was a clear penalty,' said Ferguson. 'He was definitely brought down. But we're not going to get the decisions in these big games I'm afraid.
'Obviously it gives Chelsea a major chance now and that's what happens. They got great decisions (against Tottenham on Saturday) but we never seem to get these kind of decisions.'
Ferguson's latest comments will be scrutinised. However, because he did not question Foy's integrity - as he was deemed to have done with Martin Atkinson at Chelsea in March - Ferguson is likely to escape another punishment.
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