Yoane Wissa’s first-half strike coupled with a Bryan Mbeumo double was enough for Thomas Frank’s men, who extended their unbeaten record in London derbies to 11.
The Bees continue to adjust to life without Ivan Toney but did not look back after an impressive display from their frontmen who sealed a deserved three points away from home.
Both sets of supporters set the tone as Fulham’s new striker Raul Jimenez enjoyed defending Mathias Jensen’s attacking throw-ins before the Mexican nearly caught goalkeeper Mark Flekken napping with the ball at feet.
Marco Silva had discussed the striker’s plethora of attributes on Friday and his compliments seemed justified as the £5.5million man had multiple touches of the ball in dangerous areas as the hosts pushed to capitalise on a chaotic start from both sides.
Frank’s change of shape from a back five during their 2-2 draw to Spurs to a back four here failed to resolve his side’s possession problems in the first half but a loose ball in midfield saw the pacey Wissa test Bernd Leno after 25 minutes.
After Ethan Pinnock directed a Fulham corner onto his own crossbar, Mbeumo delivered a golden opportunity to Wissa after 38 minutes but the Congo attacker scuffed his effort wide from a position you would back the suspended Toney to convert from.
But just before half-time Wissa did not have to be asked again as he gave his side the lead.
Kenny Tete’s back pass to Issa Diop saw the Frenchman fumble his touch before the Brentford attacker pounced on the loose ball and run through on goal where he dispatched his effort calmy past a helpless Leno.
Fulham responded well after the break as Tete marauded forward before his cut back found Bobby De Cordova-Reid, whose first-time effort cannoned off the crossbar as the Jamaican was denied his second of the season after his winner at Goodison Park last week.
Typical of a derby, Brentford immediately went down the other end in numbers and Jensen’s 54th-minute half-volley was hit into the ground and forced Leno to make an acrobatic save.
But in the 64th minute Wissa wreaked further havoc on the Fulham backline and forced a clumsy challenge from skipper Tim Ream, who gave away a penalty and was shown a second yellow by referee Darren Bond.
Mbeumo scored a penalty for the second week in a row after his composed effort rooted Leno to the spot as the ball clipped the inside of the left post and nestled in the bottom corner to give Brentford a 2-0 advantage.
Fulham hunted for a way back during nine minutes of added time through cameos from Willian and new signing Adama Traore but the extra man paid dividends for the visitors and Kristoffer Ajer’s well-timed cross found the potent Mbeumo who rounded off victory for Brentford.