The visitors got off to a blistering start thanks to Damien Duff's sharp finish inside three minutes from a short Bryan Ruiz free-kick but sanity was soon restored as Robin van Persie, making his first start for his new club, levelled in sensational style in the 10th minute.
Patrice Evra supplied a lovely ball from the left for the Dutchman to brilliantly fire home on the half-volley, igniting the Red Devils fans.
Things got better for United's new boys in the 35th minute when van Persie's fellow summer signing Shinji Kagawa was in the right place at the right time to tap home Tom Cleverley's saved effort.
This kicked last season's runners-up into gear and soon enough there was a third goal when Ashley Young sat up a dangerous ball from the left side of the area for an unmarked Rafael to head home at the back post.
Just when things looked like they were comfortable for United, a calamitous defensive error in the 64th minute allowed Fulham to get back in the contest at 3-2. Matthew Briggs' speculative cross form the left hung up in the air for David de Gea to come out and own it but he was weak in his aerial effort, leaving captain Nemanja Vidic to try and clear himself with the ball hitting the heel of the centre-half and trickling into the back of the net.
There were plenty of chances for both sides throughout with de Gea making a neat double save late in the first half to deny Duff and then deflecting Mladen Petric's shot onto the crossbar with Bryan Ruiz missing the follow-up from pointblank range.
With 20 minutes remaining, the Spaniard was again busy to keep out Moussa Dembele's swerving shot from range moments before he came up with a reaction save to again thwart the Belgian.
In the end, however, the scoreline was enough for Sir Alex Ferguson's men to secure their first lot of maximum points for the season whilst Martin Jol will head back to London thinking what might have been after a very strong start and a few good chances during the 90 minutes.
Old Trafford, Manchester - 75,352
Yellow cards:MU - nil FUL - Brede Hangeland 35'