The 35-year-old striker, who earlier in the week scored a nine-minute hat-trick against Bolton, pounced after 19 minutes at White Hart Lane, slotting home Darren Anderton's low cross to give Spurs the lead against their London rivals.
Ferdinand then turned provider to set up the second goal for Anderton, who finished with aplomb from the edge of the box after 39 minutes.
Simon Davies added the third after 70 minutes when he latched on to Anderton's pass and also delivered a cool finish.
Substitute Sergei Rebrov wrapped up an impressive win seven minutes later after being set up by Teddy Sheringham.
But it was the 10th goal of the season for Ferdinand, who passed a late test on a niggling ankle injury to play today, which will make the headlines.
Steffen Freund won a tackle and the ball rebounded to Davies on the right flank. He played a first-time pass into the path of Anderton, and the England midfielder picked out Ferdinand with a low cross into the six-yard box which he comfortably slotted home.
The veteran star is one of the few players who have scored more than 100 Premiership goals in his career and is in a rich vein of form, having grabbed a hat-trick of headers against Bolton in a 6-0 Worthington Cup win on Tuesday.
You could not keep Ferdinand out of the action. After 37 minutes he clashed with Sylvain Legwinski as they jumped for the ball and, although it looked an innocent enough challenge, Tottenham's man of the moment was booked.
But Ferdinand was smiling again two minutes later as he played a major role in setting up Tottenham's second goal.
Skipper Sheringham - playing the 700th match of his career in domestic football - nodded the ball to Ferdinand in the box and he held it up nicely before teeing up Anderton to rifle a low drive past giant Dutch goalkeeper Edwin van der Sar.
Just as Spurs boss Glenn Hoddle predicted, this was an enjoyable tactical battle for the neutral observer.
It was fast and furious in the early stages, with Spurs putting together some neat passing moves, while Fulham tried to hit them on the counter-attack.
One sweeping Spurs move after seven minutes involved an exchange of passes between Ferdinand, Mauricio Taricco and Gus Poyet, with van der Sar saving at the feet of the former Uruguay international midfielder in his six-yard box.
There was a bizarre incident after 28 minutes. Steed Malbranque fouled Freund but referee Neale Barry got it all wrong as he booked Louis Saha by mistake - and that despite consulting one of his assistants.
Fulham should have pulled one back in first-half injury-time. Steve Finnan's low cross from the right was missed by Chris Perry, but Barry Hayles blasted over from 12 yards.
Another good chance went begging for the visitors after 61 minutes as Finnan crossed from the right and Hayles headed wide.
Hoddle made a change a minute later, resting Ferdinand and replacing him with Sergei Rebrov.
It was Rebrov who scored the first goal in Tottenham's 2-1 Worthington Cup win at Craven Cottage at the end of last month, and he had just less than half an hour to make another impression.
Some of Tottenham's rapid passing was a joy to watch and they were good value for their lead. They were rewarded with a third killer goal after 70 minutes.
Anderton found Davies with a lovely pass on the right, and the young Welsh international cut inside two defenders and tucked the ball inside the near post.
It must have been a shock for Jean Tigana's men, having had three goalless draws in their previous four league matches.
But they had not won at White Hart Lane since 1948, and they were struggling to contain a Spurs side in irresistible form.
Having scored six goals on Tuesday, Spurs took their goal tally to 10 in five days when Rebrov scored the fourth of the game after 77 minutes as Fulham fell apart.
He was released by Sheringham and showed bags of confidence as he won his one-on-one battle with the goalkeeper.
There was time for Poyet to be denied from close range by a good save by van der Sar after 84 minutes.
The final humiliation came three minutes later when Luis Boa Morte took a tumble in the box as he was challenged by Ledley King - and was booked for diving.