Tottenham 2 Aston Villa 1
Spurs had won their previous 11 home games but a draw, the result of the three previous meetings between these two teams, looked likely until Defoe pounced.
Gareth Barry pulled one back but Spurs held on and were grateful of the partnership Defoe and Dimitar Berbatov have created in the absence of Robbie Keane and Mido.
Berbatov created both goals and could have added to his own tally for the season in a clash which came to life in the second half.
Aston Villa, meanwhile, have not won in eight matches.
Defoe, back for Spurs after missing the defeat at Newcastle with a knee injury, was lively in a first half short on quality.
The England striker was in the action immediately, having shots blocked by Craig Gardner and then Gareth Barry, then later in the opening half dragging an effort wide.
At the other end, Gardner seized on poor control by Michael Dawson to slip the ball through to Gabriel Agbonlahor early on, but Ledley King dashed back to make the tackle.
Agbonlahor's opportunity was a rare sight on goal for either side as both sides struggled to retain the ball.
Passes were a yard or two away from causing danger, and it took 18 minutes for the first save of the match.
Tom Huddlestone, with an eye for the spectacular this season following his goals against Port Vale and Manchester City, tried his luck again from long-range but Gabor Kiraly helped the ball over the crossbar.
Gardner forced Paul Robinson into a save midway through the first half with a long-range drive after Barry had cut in from the left, but the England goalkeeper was not put under too much pressure following his blunder at St James' Park at the weekend.
Berbatov almost took advantage of indecision in the Villa defence but he could only poke straight at Kiraly as the visitors backed away. Aaron Hughes was carried off on a stretcher when he collided with team-mate Olof Mellberg trying to stop the Bulgaria striker. Liam Ridgewell was brought on as a replacement.
Mellberg also needed treatment but played on until the break and helped keep Spurs at bay as they built a little momentum.
The centre-back slid in on Defoe as the striker looked to get a shot away from the edge of the area. Defoe then fired wide after latching on to a deft flick from Berbatov.
Berbatov then had an effort saved by Kiraly after Huddlestone had chipped over the Villa defence to release his team-mate.
Didier Zokora almost found Berbatov with a cross in first-half injury time, but the deadlock remained unbroken at the break.
Mellberg was replaced by Wilfred Bouma at the break, while Stiliyan Petrov was taken off for Isaiah Osbourne.
Milan Baros had a shot blocked by King on the edge of the area, while Osbourne sliced wide from a similar position.
Spurs, however, were ahead in the 58th minute when Berbatov wriggled free in front of the Villa the defence then slid the ball through to Defoe, who finished calmly for his 11th of the season.
Gardner surged forward midway through the second half in search of the equaliser, and Malbranque had to time his tackle perfectly to avert the danger.
Defoe doubled the lead, and his own tally for the day, when he controlled a Berbatov flick-on and lashed in at the near post.
Barry pulled one back with 10 minutes remaining when he held off Dawson and finished past Robinson, but Spurs held on for the spoils.
Defoe could have sealed a hat-trick late on but Kiraly saved. The striker was substituted for the final two minutes.
Jermain Defoe proved the difference as Tottenham extended their White Hart Lane winning streak with a 2-1 victory over Aston Villa, leaving his manager Martin Jol full of praise for the striker.
Defoe took his tally for the season to 12 with two goals against Villa, one of a number of clubs he has been linked with during more frustrating times for the England international.
Spurs' run of wins at home now stands at 12 too, although a draw looked likely until Defoe's second-half double.
Jol said: 'He was the difference. Simple.
'Jermain was probably the sharpest player this season, that is why he started most of times.
'There was no other option today - Mido was injured and Robbie Keane was injured. Of course he's got a run and I feel that will be the case for other strikers.'
When asked if he would sell Defoe, Jol said: 'Never.'
The Dutchman added: 'Three weeks ago Aston Villa were going for Robbie Keane, yesterday they were going for Jermain Defoe, probably next week they will go for (Dimitar) Berbatov as well so it's probably very expensive!'
Villa have now failed to win in eight matches and boss Martin O'Neill hopes confidence is not draining after a positive start to their season.
'We've got to be careful, the younger players are learning and having to learn pretty quickly,' said O'Neill.
'The goalkeeper has kicked the ball 80 yards, Berbatov has flicked it on and Defoe is in on goal - it's terrific for Tottenham but debilitating for us because if they walked it through us and smashed in a great goal I would hold my hands up. But that was poor.'
When the younger players lose a few games, what you don't want is for them now to go on the field with no confidence. It's a balancing act.
O'Neill is looking to add to his squad when the transfer window opens next month.
He added: 'The squad has been a bit weak. I knew that in August and we were unable to do anything about it at that stage.
'Obviously in January we'll hope to try to do something to give these players a bit of help.'