Spurs had drawn two and lost one of their three previous league matches this term under Villas-Boas.
And doubts were starting to surface at White Hart Lane as to whether the Portuguese, sacked by London rivals Chelsea before they won the Champions League last season, was the right man to replace the popular Harry Redknapp.
Defoe gave Spurs an 18th minute lead at the Madejski Stadium on Sunday when he stroked in a pull-back from Aaron Lennon after a burst down the right flank by the winger.
Spurs, who climbed several places to 10th spot in the table, nearly had a second goal when an error by novice keeper Alex McCarthy, dwelling on the ball in the box, saw him dispossessed by Defoe.
Defoe cut the ball back for Gylfi Sigurdsson but the Iceland international was denied on the line by Alex Pearce.
At half-time, Premier League newcomers Reading, who remained second bottom with just one point from three matches, could consider themselves fortunate to be only 1-0 down.
But, with such a slender deficit, the Royals were still in the game.
And that remained the case until 19 minutes from time when Gareth Bale finally gave Spurs the second goal their dominance deserved.
Kyle Walker's cross found Bale and the Wales star's scuffed shot beat McCarthy, already committed to a dive.
Having made it 2-0 in the 71st minute, Spurs added a third three minutes later when Defoe, on the break, beat McCarthy with a shot into the far corner.
However, Tottenham were denied a clean sheet when Hal Robson-Kanu pulled a goal back for Reading in the closing moments.