Defoe made Ramos pay for ditching him in January by scoring his fifth goal of the season as Pompey bounced back from two heavy defeats.
England striker Peter Crouch, who began his career as a junior at White Hart Lane, also helped himself to his first Premier League goal at Fratton Park.
Defoe had the ball in Heurelho Gomes' net after only two minutes when he latched onto Crouch's flick but the goal was ruled out for offside.
Gomes produced two superb saves in a matter of minutes to deny Portsmouth midfielder Richard Hughes his first ever Premier League goal.
Roman Pavlyuchenko should have scored his first Premier League goal in the 25th minute.
David Bentley found space on the right and whipped in a teasing near post cross but the Russian couldn't make a clean connection and the ball trickled harmlessly across the penalty area before Jamie O'Hara shot straight at David James.
Portsmouth were gifted the chance to take the lead 11 minutes before half-time when Jermaine Jenas needlessly handled Glen Little's free-kick, leaving referee Mike Dean no option but to award a penalty.
Defoe stepped up to hammer the ball past Gomes and into the bottom right-hand corner of the net to register his 12th goal in 18 games since his £7.5million move to Fratton Park.
Tottenham should have had a penalty of their own soon after half-time when Lassana Diarra controlled O'Hara's cross with his right arm in front of the referee but the Merseyside official waved away the visitors' appeals.
Former Liverpool star Crouch put the game beyond Spurs 22 minutes from time after a blunder by Gomes.
Armand Traore was given far too much freedom on the left edge of the penalty area and Gomes could only palm his close-range shot straight into the path of Crouch, who headed home from two yards out.
Portsmouth's joy was marred by the late dismissal of Diarra who was handed a second yellow card for a reckless lunge on Benoit Assou-Ekotto.