The England striker slotted home his 22nd goal of the season after a terrible error from stand-in Newcastle goalkeeper Steven Harper late in the first half.
It was sweet revenge for Spurs, who were knocked out of the FA Cup by the same scoreline at Newcastle last month.
Attentions for Graeme Souness' men will now turn to a big seven days where they face Sporting Lisbon and Manchester United in the UEFA Cup and FA Cup respectively.
But the last week is one they will want to forget - which included the brawl between Lee Bowyer and Kieron Dyer. Boss Souness was only interested in looking ahead. "It's a big few days for us," he insisted.
Newcastle were without the banned Bowyer and Dyer. They were also missing the suspended Stephen Taylor, and injured trio Patrick Kluivert, Titus Bramble and keeper Shay Given.
And their deficiencies showed. But despite looking the more lively side, Spurs failed to seriously worry the Geordie faithful early on.
Ironically, the best early chance fell to the visitors in their first meaningful attack. Jermaine Jenas' inch-perfect cross found Shola Ameobi unmarked at the far post but his downward header bounced up and over the bar.
Just as an uneventful opening period appeared to be coming to a scoreless end, Spurs went in front thanks to Harper's error.
His attempted clearance from Celestine Babayaro's back-pass cannoned off Simon Davies and fell to Defoe with the goal gaping – and the former West Ham star made no mistake.
But after the match Souness refused to blame Harper for his costly mistake, saying: "These things happen when you are playing reserve team football every week. It's hard to keep up with the pace once you're in the first team."
The second half assumed the same pattern – with Spurs dominating but only carving out one decent opportunity.
The biggest cheers of the day – other than Defoe's goal – came when Davies roasted former Spurs captain Stephen Carr down the left flank, much to the delight of the Tottenham fans.
But Newcastle should have been level 12 minutes into the second half. Spurs goalkeeper Paul Robinson and England colleague Ledley King got in a muddle and James Milner, who replaced injured skipper Alan Shearer at half-time, chipped woefully wide with Robinson out of position.
Souness said: "It was a game of two goalkeeping mistakes. Spurs took their chance but we didn't take ours."
Next up it was Freddie Kanoute's turn to hang his head in shame after a glaring miss. He could have sealed the points with 15 minutes left, but ballooned a shot over when through on goal after a slick pass from strike-partner Defoe.
Spurs kept Newcastle at bay for the remaining minutes, despite a flurry of late set-pieces from the visitors which came to nothing.
Tottenham boss Martin Jol was upbeat after the result, saying: "We are not playing as well away from home so it's important to get the win at home.
"If we can pick up a few more wins we have a chance of getting into Europe."