The striker's first treble for England and a late strike from Manchester City youngster Adam Johnson sealed the Group G points for Fabio Capello's side, who were desperate to bounce back from a disappointing 2010 FIFA World Cup™.
Capello kept faith with seven of the side who started the disastrous 4-1 defeat against Germany which ended their South African campaign.
The Italian supremo's trust was largely rewarded on an evening at Wembley where the pluses more than outweighed the minuses, with a revitalised Wayne Rooney helping set up all four goals.
As well as the razor-sharp finishing of Defoe, Capello could also reflect with satisfaction on an authoritative performance in goal by Manchester City's Joe Hart, who pulled off a string of key saves at crucial moments.
The emphatic win was just what Capello had been looking for as he prepares to take his side to Basle next Tuesday for a tricky away tie with Switzerland.
A menacing chip from Rooney found Ashley Cole darting into the box, whose shot was well stopped by Nikolay Mihaylov at the near post. Mihaylov was only able to divert the ball back to Cole, however, and the Chelsea left-back steered the rebound back across the six-yard area for Defoe to hook it into the roof of the net.
Capello's men kept Bulgaria pegged back throughout the opening 45 minutes, closing down their jittery opponents with vim and vigour. Yet for all England's dominance of possession they were unable to add to Defoe's early goal.
In fact, the closest an England player came to scoring again in the first half came at their own end, when Hart cemented his status as Capello's first-choice goalkeeper with a fine save from a miscued Glen Johnson clearance.
England were back on the attack within moments of the restart, however, and Rooney forced a scrambled one-handed save from Mihaylov with an audacious lob from the edge of the area.
But Bulgaria also had alarm bells ringing at the other end when Spurs centre-half Michael Dawson allowed Valeri Bojinov to sneak in after misjudging a speculative punt forward. Bojinov threaded through to Ivelin Popov, whose rasping shot across the face of goal flew just wide with Hart beaten.
Bulgaria's next attack would lead to the decisive England goal on 61 minutes. A swift break out of defence freed winger Martin Petrov in space down the left. Petrov's cutback was met first time by Stanislav Angelov only to be parried by Hart, and as Bulgaria rued missing what would have been a well-worked equaliser, England raced forward on the counter-attack.
Gerrard broke and the ball was rapidly swept to Rooney, who once again turned provider to slide a perfectly-weighted pass through to Defoe, who finished calmly to seal the match.
The increasingly assured Hart again thwarted Bulgaria moments later, producing a splendid one-handed save from Stanislav Rangelov.
Johnson drilled in number three on 83 minutes after good work by Rooney, before Defoe - played in by Rooney once more - completed his hat-trick.