Zamora's five-minute double salvo proved the catalyst as the Cottagers climbed into the top half of the table.
The 30-year-old showed great composure to latch onto a wayward James Beattie pass and smash home in the 23rd minute before heading home Damien Duff's right-wing free-kick five minutes later for his first goals since August - which also came against the Tangerines.
Dickson Etuhu settled the result with a 72nd-minute tap-in to secure Fulham's fifth home win in six matches.
The game also proved a welcome return to footballing action following the unveiling of the much discussed - and in some quarters maligned - Michael Jackson statue prior to the game by chairman Mohamed Al Fayed.
Heading into the 100th league meeting between the pair, the hosts were boosted by Zamora's recovery from illness and Steve Sidwell's return to the squad after a knee injury.
Blackpool manager Ian Holloway made two changes to the side that drew 2-2 at Blackburn a fortnight ago, with Beattie and Brett Ormerod replacing Luke Varney and Jason Puncheon in the starting line-up.
It was the home side who controlled the opening proceedings, with Moussa Dembele regularly testing Alex Baptiste down the left and skipper Danny Murphy seeing a low drive blocked.
Charlie Adam blazed over Blackpool's first chance in the ninth minute, although his 35-yard effort never looked like it would add to his nine-goal haul this season.
Despite the midfielder's shot, it was Fulham who were looking the most dangerous and hit the post in the 16th minute.
Carlos Salcido's left-wing cross was headed back by Zamora to Dembele, whose superb lay-off was met by an equally well-struck shot by Duff that goalkeeper Richard Kingson did well to tip onto the woodwork.
Fulham again came close to breaking the deadlock five minutes later but Kingson was on hand to block another drilled shot, this time Chris Baird the man denied.
However, the Ghana international could do nothing to prevent Zamora's smashed drive in the 23rd minute as he latched onto Beattie's poor backpass and ran clear before finishing with aplomb.
Fulham continued to threaten and Zamora netted his second of the afternoon five minutes later.
The England international out-leaped Craig Cathcart in the six-yard box to nod in Duff's whipped free-kick, to the delight of the home faithful.
However, the crowd's exuberance was tempered somewhat in the play that followed as the visitors began to get a foothold in the game and started to open up the Fulham defence.
After thwarting the visitors, Fulham's calls for a 38th-minute penalty were waved away by referee Stuart Attwell, who deemed Stephen Crainey's slide on Duff hard but fair.
The pace of the game began to drop as half-time approached, but Blackpool came desperately close to reducing the deficit just before the break.
Ormerod beat Mark Schwarzer to Baptiste's long ball, but his goal-bound header was cleared off the line by former Southampton team-mate Baird.
The game livened up in the 57th minute, with Dembele's neat touch and turn followed up by a 20-yard drive that Cathcart did well to block.
Beattie came close to atoning for his earlier error, but his powerful shot clattered off the post.
The former England international was soon replaced as Holloway made wholesale changes in a bid to change the game.
Off came Beattie, Ormerod and Elliot Grandin to be replaced by Sergey Kornilenko, Varney and Puncheon.
And Holloway's move almost paid immediate dividends as the latter found space to test Schwarzer with a powerful 20-yard drive.
However, Fulham soon wrapped up the victory with their third of the afternoon through Etuhu.
Murphy's free-kick was thumped off the post by Clint Dempsey and the rebound was fired across goal by Brede Hangeland for Etuhu to net.
Having earlier taken off Zamora, the goal allowed manager Hughes to replace Murphy with Sidwell - making his first appearance since February.
Duff also soon departed to be replaced by Simon Davies, before Aaron Hughes and substitute Kornilenko clashed heads on the halfway line.
While the players received treatment, fans were treated to a Jackson tribute by a fan in the stands in what proved to be the last notable entertainment of the match.