Frank Lampard struck twice as Chelsea tightened their grip at the top of the Premiership table. Lampard scored from the spot six minutes before half-time after Alexei Smertin was fouled by Ledley King.
And he rounded off another impressive Chelsea win in injury-time when he fired home after good work by substitute Eidur Gudjohnsen.
Spurs rarely threatened as Chelsea made it 18 years without a league defeat at White Hart Lane.
Spurs were without Freddie Kanoute, who had failed to recover from a hamstring injury.
Chelsea made five changes from the Carling Cup semi-final against Manchester United, with Arjen Robben, Didier Drogba, Petr Cech, Glen Johnson and Smertin all coming back.
Defoe demonstrated the talents that have had him linked with a move to Chelsea early on.
He cut inside and unleashed a shot from the edge of the area, which took a deflection off Damien Duff but was well blocked by Cech.
Chelsea's response was a lob from the dangerous Drogba, that looped over onrushing Spurs goalkeeper Paul Robinson but drifted agonisingly wide.
But the league leaders went ahead in controversial circumstances six minutes before the interval.
Smertin tumbled under a challenge from King and Spurs were furious when referee Graham Poll pointed to the spot.
Lampard ignored the protests to calmly beat England colleague Robinson.
Spurs had acquitted themselves well against Mourinho's side, who were fortunate to escape when Smertin flashed a header narrowly wide of his own goal.
And, as Spurs pressed forward, Chelsea broke and substitute Gudjohnsen set up Lampard for a powerful finish from the edge of the box.