Berbatov notched the only goal with a superb back-post header in the 80th minute to extend manager Juande Ramos' unbeaten run to eight games.
Pompey have now gone five league and cup games without a home win.
Portsmouth had the first sight of goal after only six minutes when Tottenham old boy Pedro Mendes played through John Utaka with a clever chipped pass.
Utaka made a hash of his first touch and fired a weak shot straight into the arms of Spurs goalkeeper Paul Robinson.
Spurs should have taken the lead in the 17th minute when Kevin-Prince Boateng passed up a golden chance for his first Premier League goal.
Aaron Lennon found himself in yards of space on the right before pulling the ball back for Boateng, who slipped as he shot left-footed and allowed David James to save on the line.
Steed Malbranque hammered the rebound into James' empty net but the goal was rightly ruled out for offside.
Sulley Muntari was Pompey's two-goal hero at Aston Villa last weekend and the Ghanaian tested Robinson's reaction with a 25-yard deflected free kick midway though the first half.
James almost gifted Tottenham the lead nine minutes into the second half when he punched Lennon's dangerous cross against defender Glen Johnson, but Noe Pamarot got back to spare Johnson an embarrassing own goal.
Substitute David Nugent must have thought he had ended his long wait for a first Premier League goal when he was picked out by Niko Kranjcar's 70th minute corner only to head onto the roof of the net from six yards.
Berbatov showed Nugent how it should be done ten minutes from time when he won the match for Spurs.
Lennon whipped in a teasing cross from the right and Berbatov escaped marker Sol Campbell to nod home at the back post.