Premier League - Fulham send Wigan bottom
Wigan dominated possession but were by and large toothless up front. Dempsey's 41st minute close range strike gave Fulham the lead against the run of play before Dembele calmly side-footed home the clincher three minutes from time.
It was Fulham's first away win of the season, and only their second in total this season, and moves them up one place to 16th in the table.
Wigan are now bottom on goal difference though after previous incumbents Blackburn picked up a point at Norwich to overtake them.
Both teams named unchanged line-ups despite defeats last weekend and Fulham produced the crisper passing in the open exchanges.
Wigan also received an early blow when Mohamed Diame was on the wrong end of a heavy challenge from Steve Sidwell in just the third minute. He tried to run off the knock but was forced off in the 12th minute with what looked to be an ankle injury and was replaced by James McArthur.
Wigan however, soon got a foothold on proceedings and proved to be the better side for the majority of the half, finding particular joy down the right wing.
Their two best chances came within a minute of each other just past the half-hour mark. First Ben Watson saw his decent half-volley from the edge of the area tipped over by Mark Schwarzer and then from the resulting corner Gary Caldwell headed over when he should have at least hit the target.
Danny Murphy produced a superb long cross-field ball in behind the Wigan defence that put Zamora free down the left. The England striker was then able to run to the edge of the box before rolling a simple ball across the face of the goal for the onrushing Dempsey to side-foot home from close range.
It was Dempsey's 36th Premier League goal, equalling the American record for goals in the division that had previously been held solely by another former Fulham man Brian McBride.
The second-half had a similar feel to the first with Wigan pinning Fulham back but without testing Schwarzer with nearly enough regularity.
The Australian keeper was beaten in the 54th minute by a lovely dipping half-volley from the lively Victor Moses but the ball cannoned off the crossbar to let Fulham off the hook.
At the other end Zamora hit the bar in the 62nd minute after another long range ball from Murphy cut open the defence and the woodwork was struck for a third time when Maynor Figueroa's long range strike in the 84th minute clipped the outside of the post.
Wigan's confidence though seemed to drain as the match went on and their hope completely evaporated three minutes from time when Dembele wrapped it up.
The Belgian pounced on a loose ball in midfield and ran towards the edge of the area unchallenged; then as the whole ground waited for him to slip the ball into the unmarked Dempsey, he decided instead to casually stroke the ball into the corner of the net to seal all three points.
The DW Stadium was half-empty to begin with but was virtually deserted in stoppage time when Caldwell blazed over the bar from close range.
Wigan next face what some might already say is a relegation six-pointer at Wolves while Fulham host Wisla Karkow in the Europa League on Thursday before welcoming Tottenham to Craven Cottage three days later.