After being held to a goalless draw at Ninian Park ten days ago, Tottenham were determined to book a home date against Southend United in the next round.
Cardiff must have fancied their chances, especially after Tottenham suffered a 3-2 home defeat against Newcastle on Sunday.
But the north London side showed all their Premiership class to ensure they kept alive their dreams of reaching the first FA Cup Final back at the new Wembley in May.
The Premiership side dominated the opening exchanges and could have broken the deadlock after just ten minutes when Dimitar Berbatov fired a blistering drive which flew inches past the post.
Ivory Coast international Didier Zokora then came close on 15 minutes when he made space for himself and unleashed a 25-yard shot which also flashed just wide of the goal.
The home side continued to mount pressure on the Cardiff goal and Michael Dawson rose the highest in the box to meet a cross from Tom Huddlestone, but his close-range header fell the wrong side of the post.
Tottenham were finally given their just rewards when Lennon opened the scoring on 27 minutes. The England winger played a clever interchange with Zokora and narrowly beat the offside trap before slotting the ball past Cardiff keeper Neil Alexander.
Keane doubled Tottenham's lead on the half-hour mark. Berbatov skipped past Cardiff defender Glenn Loovens before cutting the ball back for the Republic of Ireland international.
Keane, who had only just returned from a knee injury, made no mistake striking the ball into the roof of the net.
Things were threatening to get out of hand for Cardiff when Malbranque added a third on 42 minutes. Benoit Assou-Ekotto fed the ball into the path of the French midfielder, and he gave Alexander no chance with a blistering drive which sailed into the corner of the net.
Defoe wrapped up a convincing victory when he scored Tottenham's fourth on 81 minutes. Substitute Hossam Ghaly saw his shot beaten out by Alexander but the rebound fell straight to Defoe who tapped the ball home at the second attempt.
Tottenham now face Southend in the fourth round at White Hart Lane on January 27.