Carlos Tevez scored twice and Wayne Rooney and Park Ji-sung also struck as United turned on the style at Craven Cottage, while goals from Didier Drogba and Alex made it six wins out of six since new manager Guus Hiddink arrived at Chelsea.
United boss Alex Ferguson, eyeing next week's Champions League return with Inter Milan and Premier League showdown with Liverpool, opted to leave Cristiano Ronaldo and Dimitar Berbatov out of his squad but in Tevez he had the ideal replacement.
The Premier League leaders survived a couple of scares as Fulham started confidently but once they took the lead with a Tevez header in the 20th minute United were in a different class.
Tevez advanced towards the Fulham box and unleashed a swerving shot that flew beyond goalkeeper Mark Schwarzer in the 35th for a superb second.
United put the game to bed five minutes after the restart when Rooney clipped a low shot into the corner after another exchange with the tireless Tevez and Park rounded things off with an almost identical finish nine minutes from time.
"It was a superb performance from Carlos Tevez," Ferguson told MUTV. "He was like a jack-in-the-box all day and he showed great energy, getting on the ball and showing great movement.
"His second goal, in particular, was fantastic.
"Right from the word go all the players played with great energy and enjoyment."
DANGEROUS CHELSEA
Hiddink sent out a full-strength side despite the looming second leg of Chelsea's Champions League last-16 tie at Juventus on Tuesday and his team were dangerous from the start.
They opened the scoring after 15 minutes when Drogba muscled Scott Dann off the ball, went round keeper Kieran Westwood and turned in his shot from a tight angle.
Championship (second division) team Coventry, seeking to reach the last four for the first time since winning the Cup for the only time in 1987, struggled to build any pressure and it was no surprise when they fell further behind after 72 minutes.
Alex and Drogba, who had both been off the pitch receiving treatment after a collision, came back on and immediately joined a counter-attack that ended with halftime substitute Ricardo Quaresma crossing for the Brazilian defender to sidefoot home.
Chelsea also enjoyed the added bonus of a first appearance since August for midfielder Michael Essien, who played the last 30 minutes having recovered from a knee ligament injury.
On Sunday Everton host Middlesbrough in another quarter-final while Arsenal play Championship side Burnley, the only remaining non-Premier League club, in a delayed fifth-round tie.
