Goals from Jermaine Pennant and Peter Crouch saw Liverpool put a major dent in Fulham's survival hopes.
Pennant gave the Reds the lead against the run of play when he was put through by Lucas Leiva and he took Kasey Keller by surprise with a powerful early shot.
He then turned provider to set up Crouch to score with a low drive.
Fulham were restricted to mostly half chances, with midfielder Danny Murphy going closest with a shot denied by Pepe Reina's legs.
Victory strengthened Liverpool's grip on fourth place - they are now eight points clear of Everton with three games left - but Fulham are five points adrift of safety and staring relegation in the face.
Reds manager Rafael Benitez caused a storm a year ago by naming a weakened side that lost at Craven Cottage and went a long way to keeping Fulham in the top flight.
With a Champions League semi-final again occupying his mind, he made eight changes.
And after 10 minutes he looked like he might be incurring the wrath of more relegation strugglers as his new-look side were second best.
But Fulham were unable to carve out a goalscoring chance and their mini spell of dominance was pegged back by Pennant's growing influence.
He produced an inch-perfect cross for Crouch to stoop and head just off target before he broke the deadlock with a goal created by Andriy Voronin and Lucas.
Lucas played the final ball through to Pennant, who shot powerfully from the edge of the area and Keller could only watch it fly into the net.
Fulham had chances to level before half-time but Brede Hangeland headed past the post and Brian McBride fluffed his volley from a punt forward by Keller.
At the other end Liverpool could and should have added to their advantage as their new-look side started to find their feet with some crisp passing moves.
The lively Pennant was frequently involved and he crossed for John Arne Riise only to see his effort cleared by Paul Stalteri with Keller stranded.
There were further chances for Voronin and Yossi Benayoun and it was looking only a matter of time before Liverpool had the points sewn up.
Clint Dempsey, who got the winner in the controversial fixture last season, almost upset the apple cart when he twice went close with headers but he lacked direction on both occasions.
Liverpool earned some breathing space with a second goal with 20 minutes remaining.
Fittingly, it was created by Pennant, who slipped the ball in for Crouch to run on to.
The big striker was given time and space to fire in a low shot, but even then Keller should have perhaps done better than deflect the ball in off his legs and into the net.
Danny Murphy could have caused his old club some difficult moments but his shot was kept out by a smart block by Reina.
Fulham kept plugging away until the bitter end with Dempsey seeing an effort deflected just past the post in injury-time.
But Liverpool's biggest worries were keeping their players fit for the game against Chelsea, with Sami Hyypia withdrawn at half-time with a head injury and Javier Mascherano hobbling off.
• Fulham manager Roy Hodgson:
"We matched them quite well but once they got their first goal we were chasing the game and when they got the second goal it put us out of contention.
We can retain hope of staying up. The task gets harder because we have not recovered any points on the teams above us and we have lost another game and another opportunity.
"We have given a good account of ourselves but we do not have anything to show for it."
• Liverpool manager Rafael Benitez:
"I picked a team I believed could win the match. We now need just one more point to ensure fourth place in the league, even if Everton win all their remaining games.
"We can completely focus on the game against Chelsea now. We've talked a lot about boardroom matters for a long time but for now I just want to speak about football, if that's possible.
"Javier Mascherano took three knocks but I think he will be okay."
Fulham: Keller, Stalteri, Hughes, Hangeland, Konchesky, Davies, Bullard, Murphy (Andreasen 78), Dempsey, Healy (Nevland 76), McBride (Kamara 81).Subs Not Used: Warner, Bocanegra.
Liverpool: Reina, Finnan, Skrtel, Hyypia (Carragher 46), Riise, Pennant, Lucas, Mascherano (Alonso 72), Benayoun, Voronin (Aurelio 82), Crouch.Subs Not Used: Itandje, Torres.
Goals: Pennant 17, Crouch 70.
Ref: Martin Atkinson (W Yorkshire).