Tottenham rarely got out of second gear at White Hart Lane as they strolled to victory in their Group K opener, with Defoe's first-half brace proving crucial.
The 30-year-old has not started a Premier League match this season but showed no signs of lacking sharpness as he lobbed Tromso goalkeeper Marcus Sahlman with a terrific finish in the 21st minute.
And the England international scored his 20th goal in Europe for Tottenham just nine minutes later with a composed left-footed effort.
Substitute Christian Eriksen sealed the win in the 86th minute with a superb curling strike as Tottenham won well.
Injuries to Danny Rose and Moussa Dembele were the only negatives for Spurs manager Andre Villas-Boas, but this was as comfortable as victories come for the Portuguese's side.
Villas-Boas made six changes to the team that beat Norwich City 2-0 on Saturday, with Defoe, Erik Lamela, Lewis Holtby and Danny Rose among the inclusions.
It was still a Tottenham side that contained nine full internationals though, while Czech striker Zdenek Ondrasek headlined Tromso's three inclusions.
Spurs made a bright start to the match and Rose fired an early warning to the visitors when he skipped down the left flank, cut in and shot at Sahlman in just the fourth minute.
Holtby then put Defoe through with an excellent ball, but the England striker was denied by the legs of Sahlman, before Dembele and Gylfi Sigurdsson had attempts on goal.
Tottenham were in cruise control and the first goal came as no surprise, as Defoe opened his account for the evening with a clever dink.
Sigurdsson started the move by winning the ball back and a slick move finished with Defoe, after Lamela's first-time flick put him into space, and he calmly chipped over Sahlman to please the home crowd.
Younes Kaboul poked wide from a corner shortly after before Tottenham doubled their lead on the half-hour mark through Defoe again.
It was another expert finish from Defoe, who ran onto a smart Holtby ball before slotting past Sahlman with his left foot.
Sigurdsson then shot wide and Defoe had a curling effort saved as Tottenham continued to dominate.
Tromso sat back after the break, eager to avoid a thrashing, and as a result the hosts had even more time on the ball and the pace of the match dropped.
Defoe was flagged offside when a chance for his hat-trick looked likely, and Lamela and Holtby did not convert chances.
Morten Moldskred made an excellent run through the Tottenham defence but failed to produce an end product, while Fulham loanee Josh Pritchard fired over from distance for the visitors.
Tottenham's attempts for a third saw Sandro head straight at Sahlman while Paulinho had an effort blocked, before Eriksen opened his account for the club with an excellent strike from distance.
The 21-year-old curled a 20-yard effort into the top left corner, leaving Sahlman stranded to put the gloss on an easy win for the home side.
