The American took his season's tally to 21 with a superb free-kick and a firm header before Mahamadou Diarra wrapped up a convincing Premier League win at the Reebok Stadium.
Bolton paid the price for a lacklustre first-half display and remain deep in trouble after their three-game winning run was brought to an end.
They had entered the game with confidence but must now regroup quickly for a tough trip to Newcastle on Monday.
The Trotters made just one change by replacing striker Ivan Klasnic with fit-again midfielder Darren Pratley.
That meant captain Kevin Davies was again on the bench despite scoring on his last two appearances but Bolton might have done with his aggression as they failed to take an early grip.
Fulham were without veteran midfielder Danny Murphy and new strike star Pavel Pogrebnyak but were the more energetic with Damien Duff on song and Dempsey adding the cutting edge.
The game's opening exchanges were quiet and it was not until the 13th minute either side created a serious opportunity as Bolton's David Ngog broke clear on the right only for Ryo Miyaichi to side-foot over.
Duff found space outside the area to hit Fulham's first attempt on goal but his effort found only the side-netting.
Dempsey turned the ball into the net for the first time after 24 minutes when a deflected Duff shot rolled into his path but the flag was raised for offside.
But the American had better luck on the half-hour as he lined up a free-kick 30 yards out after Pratley fouled Diarra.
Dempsey was keen to take it ahead of John Arne Riise and Bryan Ruiz and justified his confidence as he connected sweetly to fire into the top corner.
Bolton were slow to respond and Fulham pushed them back again before Dempsey sliced well wide with an ambitious overhead kick.
The Trotters finally showed some intent as Marcos Alonso came forward but shot harmlessly at Mark Schwarzer from distance.
Martin Petrov then looked for Ngog with a cross but Aaron Hughes cleared and Nigel Reo-Coker also shot at Schwarzer.
Yet Fulham continued to look the more dangerous in attack and doubled their lead on the stroke of half-time as Duff beat Alonso on the outside and crossed to the back post for Dempsey to head his second.
Bolton boss Owen Coyle attempted to inject some urgency by sending on Davies and Chris Eagles for Pratley and Miyaichi at the start of the second half.
The rewards were almost immediate as Alonso was tripped just outside the area and Eagles curled a free-kick narrowly wide.
Eagles then had a fierce shot from the edge of the area blocked after the ball came back to him from a corner he had taken.
Petrov tried to control an awkward ball from Davies but volleyed wide from 18 yards as Bolton continued to press for an opening.
Eagles clipped a cross into the area but Ngog collided with Davies and could not keep his header on target.
Bolton were almost caught out as Duff again tricked his way past Alonso to get a clear sight of goal but Adam Bogdan palmed away his low strike.
Ngog beat Brede Hangeland to race towards the Fulham goal but was bundled off the ball by Riise on the edge of the area and referee Mike Dean ignored his appeals for a penalty.
Dempsey spurned a good chance to claim a hat-trick when he shot wide after finding room just inside the Bolton box.
Bolton ignored an injury to Ruiz to continue an attack but Fulham held firm.
The Costa Rican received treatment when play was eventually stopped but was unable to continue and was carried off and replaced by Dickson Etuhu.
Fulham ended the game as a contest 10 minutes from time as Riise burst clear unchecked on the left and crossed low for Diarra to slide in a third.
Moussa Dembele threatened another with a good run in the closing moments but was crowded off the ball.
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