Harlee Dean scored an own goal as Brentford were beaten at the KC Stadium.
Dean turned Andrew Robertson’s driven cross into his own net from close range just after the half-hour mark.
Robertson hit the bar and Bees keeper David Button saved a penalty before Mohamed Diame doubled Hull’s lead just before half-time.
The opening goal came after a decent start by the visitors, who were unbeaten in their previous six matches.
Brentford striker Marco Djuricin shot wide and youngster Josh Clarke fired over before Hull began to take control.
After going ahead, the Tigers were given a chance to make it 2-0 when Alex Bruce was fouled in the penalty area by Jake Bidwell.
But Button kept out the resulting spot-kick by Adama Diomande, and two minutes later saw a strike from Robertson smack against the woodwork as Dean Smith’s side tried to weather the storm.
Had they got to the interval just one goal down, their task would have been less difficult, but they never looked like coming back after Diame’s goal.
Harry Maguire found the former West Ham man, who slotted home at the second attempt after Button had saved his first effort.
Sam Saunders came close to pulling a goal back with a free-kick and brought a late save from keeper Eldin Jakupović.