Portsmouth looked to be heading for all three points after David Nugent had given them the lead just before the hour mark.
But Defoe showed why Tottenham have forked out £15million for his signature when he scored a trademark goal to lift them off the bottom of the table.
All the headlines had surrounded Harry Redknapp facing Pompey for the first time since he left Fratton Park to join Spurs in October and he received a barrage of abuse from the away supporters at White Hart Lane.
Sol Campbell also faced a cauldron of hate from the Tottenham fans, but the Pompey skipper produced a superb display to silence all his critics and ensure his side came away with something.
Sean Davis almost gifted Tottenham the lead on eight minutes when he played a long-range ball straight into the path of Defoe who was clean through on goal.
The home supporters were waiting for the prolific forward to make it a dream home start against his former club, but he fired the ball wide of the post.
Tottenham keeper Heurelho Gomes was clearly feeling the affects of a groin injury he suffered against Wigan last week and nearly produced another major howler on 12 minutes.
Gomes failed to hold onto a shot from Glen Johnson and Peter Crouch looked certain to knock the loose ball home, but the Brazilian keeper somehow managed to flick the ball away at the second attempt.
Defoe was determined to get on the scoresheet against his former club and went close again on 15 minutes when he fired a low shot which produced another fine save from James diving low to his left.
Aaron Lennon then tested James four minutes later when his dipping shot was turned around the post by the Portsmouth keeper.
From the resulting corner, Jonathan Woodgate's header was flicked into the path of Roman Pavlyuchenko whose shot looked destined for the back of the net only for it to be blocked by his strike partner Defoe.
Lennon was causing all kinds of problems for the Pompey defence and he burst clear into the penalty area on 23 minutes and crossed for Defoe whose close-range header was tipped over the bar by James.
Vedran Corluka produced an excellent piece of defending three minutes later to stop Armand Traore giving Portsmouth the lead.
Nugent broke the offside trap and cut the ball back for Traore who had the easy task of knocking the ball into an empty net, but his shot was superbly blocked by the Croatian defender.
Tottenham then suffered a major injury blow on 28 minutes when Pavlyuchenko was carried off on a stretcher and replaced by Darren Bent.
And it was Portsmouth that should have taken the lead three minutes before half-time when Nugent found himself clean through on goal, only for his shot to be kept out by Gomes' legs.
Things got even worse for Redknapp when influential skipper Ledley King was forced to leave the field on the stroke of half-time after picking up a hamstring strain. He was replaced by Michael Dawson.
Nugent made up for his earlier miss when he opened the scoring for Portsmouth on 58 minutes - his first Premier League goal for the club following his £6million move from Preston.
Traore played the ball into the Pompey forward who fired a fierce shot which took a wicked deflection off Gareth Bale and flew past Gomes into the corner of the net.
Defoe made it a homecoming to remember when he netted the crucial equaliser on 70 minutes. Luka Modric laid the ball into the path of the England forward who fired a left-foot shot through the legs of Campbell and past James.
Corluka could have grabbed a winner for Tottenham with 15 minutes left when his header was cleared off the line by Davis.
Substitute Bent blew a late golden chance to hand Tottenham all three points when Modric picked him out at the far post but, with the goal at his mercy, he somehow headed the ball wide.