The hosts put four past a Hull outfit who looked lethargic throughout the game with former Tigers forward Sone Aluko opening the scoring for Fulham just 17 minutes in.
The Yorkshire side equalised shortly after half-time through Lazar Markovic but goals from Chris Martin, Ryan Sessegnon and Stefan Johansen put the game to bed before Hull striker Abel Hernandez failed to convert two late penalty kicks at Craven Cottage.
The Londoners made four changes from the side which lost 1-0 to Reading on Tuesday with Floyd Ayite, who returned from the African Nations Cup following Togo's exit from the competition, and new signing Thanos Petsos, who joined the club from German side Werder Bremen, starting the game on the bench.
Following their exit from the EFL Cup on Thursday Hull manager Marco Silva made seven changes with Markovic, who came off the bench in midweek, awarded his first start for the club.
Silva was forced to make an early change with Harry Maguire replacing Curtis Davies after he limped off holding his hamstring and t he visitors struggled to get momentum
On 17 minutes Fulham were awarded a free-kick after Tom Huddlestone brought down Martin
Midfielder Johansen's cross into the box found the head of Tomas Kalas and Aluko fired the ball into the back of the net to score his fifth goal of the season in all competitions
The Tigers looked tired throughout much of the first half, struggling to get into an attacking position but after half-time they quickly caught the Fulham back four napping as Markovic was left unmarked to head Andrew Robertson's cross home
The goal was the midfielder's first for the visitors since he joined on loan from Liverpool on Monday
It was not long until the hosts were back in control and just five minutes later they were ahead once again
A piece of excellent play saw Sessegnon pass the ball across the Hull defence, leaving on-loan Martin, who is said to be keen to return to parent club Derby, with an easy finish into an empty net to slot the ball into.
Slavisa Jokanovic's side continued to dominate and on 66 minutes Sessegnon and Martin teamed up again with 16-year-old Sessegnon slotting the ball past Hull goalkeeper Eldin Jakupovic.
The visitors struggled to get back into the game and Fulham, who had not beaten Hull since 2009, scored again with just over 10 minutes to go
Midfielder Tom Cairney held the ball up in the area before passing to Johansen, who was left unmarked, and the 26-year-old midfielder was left with time to make sure his shot was on target
In a late twist - with less than five minutes remaining - the visitors were awarded a penalty when Kalas brought down Robertson.
Hernandez's first effort was saved by Bettinelli, but the Fulham goalkeeper fouled the Uruguayan as they challenged for the loose ball.
Hernandez stepped up to take the second penalty, but again he was denied by Bettinelli.
Source : PA