It was a welcome win on tough territory in SW6, with two superb finishes from Keane - his 2nd and 3rd FA Cup goals of the season, nine in total - really deflating the spirit of Chris Coleman's side and Berbatov providing a cushion after coming off the bench in the second half.
There was a flurry of early activity as a result of a teasing centre from Moritz Volz, but the contest really slipped into gear with just five and a half minutes on the clock from a typical Paul Robinson clearance.
It was Mido who accepted the ball first out of the sky and cleverly directed a flick into the path of Keane, who let the ball bounce without taking a touch before thumping a right-footed volley past Jan Lastuvka in the Fulham goal.
There was some alarm on 17 minutes when an Alexey Smertin cross was cradled by Brian McBride, the American proceeding to shoot on the spin and his effort pinged up off the toe of Anthony Gardner. Robinson's reactions were in fine working order!
The goalkeeper was later on high alert with a smart save to keep a Mido header out of our net, the striker reacting the wrong way to a Volz flick on.
Fulham were the livelier when the whistle sounded to get the second half underway, but our two banks of four in brown managed to stand fairly firm and keep Robinson largely untroubled. An Aaron Lennon dash on the counter was eventually thwarted by Lastuvka, before Robinson was called upon to deal with a long ranging bouncing effort from Papa Bouba Diop.
The home goalscorer from the league game a few weeks ago, Vincenzo Montella, was introduced just after the hour mark to much acclaim from the majority of those inside Craven Cottage.
The acclaim was all from the away end on 68 minutes when, from a Lee Young-Pyo free-kick from deep on the left, there was almost an action replay of the first goal. It was another flick on from Mido, but this time Keane's finish was that little bit more devilish and the ball zipped past Lastuvka and into the top corner.
A few minutes later Robinson kept the advantage at two with a superb one handed save from a Volz piledriver. It was then time for Berbatov, but it was another substitute forward in a white shirt who came close to making the next impact. Collins John was sharply onto a Diop throughball and whipped his shot just over the bar.
Berbatov did not have to wait long to make his mark on the game though, seizing onto the ball after good work from Didier Zokora after 77 minutes and curling a low shot with his right foot that came back off the inside of Lastuvka's left hand upright. Speedy to react, the Bulgarian simply stroked the ball into the back of the net with his left foot.
And he wasn't finished there. As the game ticked into added time, Keane's cushioned volley pass found his partner just the right side of the home defensive line and as Fulham waited for a flag, Berbatov calmly lofted the ball over Lastuvka and home.
The home side's woes were completed when Montella was sent off in added time for aiming an elbow at Keane.
Mobile Ringtone - Glory Glory
Text SPURS T1 to 78787
Click here to check compatability
Click here to listen
Click here to view full Mobile range
Two goals apiece from Robbie Keane and Dimitar Berbatov secured our passage to the quarter finals of the FA Cup against Fulham at Craven Cottage.