Tottenham were the better side from the first whistle in Berkshire and took the lead in the 18th minute when Defoe converted Aaron Lennon's cutback.
Reading threatened briefly either side of half-time but Spurs had regained control of the game well before Bale made it 2-0 with a scuffed finish in the 71st minute.
Defoe then scored another three minutes later after a run from inside his own half to earn Andre Villas-Boas his first win as manager but leave Reading still looking for their first success back in the Premier League.
The Royals did score a late consolation, however, when Adam Le Fondre lifted a ball to the far post for his fellow substitute Hal Robson-Kanu to poke home.
The win comes as a huge relief for Villas-Boas, who had come under fire for his management during the club's first three games of the season.
Last time out they were booed off for a dire performance against Norwich. At times Spurs looked clueless against the Canaries, but on this occasion the north London outfit put on a top-rate performance.
Mousa Dembele, Gylfi Sigurdsson and Defoe were all at the top of their game as Spurs put on the kind of performance that at times set pulses racing during the Harry Redknapp era.
Although Alex McCarthy was making his first appearance in the Premier League, he showed no nerves to deny Sigurdsson and Jan Vertonghen with two fine reaction saves after three minutes.
Vertonghen then launched a ball over the top from deep, but Bale's first touch was not quite good enough and the ball dribbled wide.
Reading thought they should have had a penalty in the 11th minute when the ball struck Kyle Walker's arm as he jumped for a Danny Guthrie free-kick, but Howard Webb ruled that Alex Pearce had fouled the right-back.
The penalty call aside, Reading were struggling to make an impression on the game.
The seemingly inevitable opener came after 17 minutes when Sigurdsson sliced open the Reading defence to find Lennon who squared for Defoe to rifle home from 15 yards.
McCarthy then had to be at his best to deny Sandro from long range as Tottenham looked for a quick second.
Defoe brilliantly took down a long raking pass from the excellent Kyle Naughton and slipped past two defenders but his toe-poke went wide.
McCarthy then almost gifted the visitors a second when he dallied on the ball on the edge of his box. Defoe pinched it off the 22-year-old and squared to Sigurdsson but Pearce rushed back to clear the ball off the line.
Another mix-up at the back gave Tottenham one more chance nine minutes before the break but Defoe over-hit a pass for Lennon.
Reading started to get in to the game more but Friedel was largely a spectator, with Jobi McAnuff's wayward shot the Royals' only attempt at goal towards the end of the first half.
Brian McDermott looked to Le Fondre for inspiration, the former Rotherham striker coming on for midfielder Jem Karacan at the break.
The change had little immediate effect, as Tottenham continued to dominate.
Dembele's deflected shot fell at Defoe's feet in Tottenham's first chance of the second half, but the England striker spooned his shot high and wide.
Kaspars Gorkss then put in a superb last-ditch tackle to cut out Lennon's cross as Bale lurked in the centre of the box.
Just after the hour Bale turned on the after-burners to sprint down the left and cross for Defoe, but the 29-year-old shot two yards wide.
Spurs moved 2-0 up with 20 minutes to go through Bale. Walker skilfully slipped past two defenders and pulled back for the Welshman, whose scuffed shot looped over McCarthy in to the net.
Any hopes Reading had of a comeback were extinguished two minutes later when a brilliant solo goal from Defoe killed off the match.
The England striker robbed Gorkss on the half way line, stormed past four Reading players on a 40-yard run before slipping past McCarthy.
The away fans, who so vocally booed Villas-Boas at White Hart Lane two weeks ago, chanted the Portuguese's name after the goal went in, clearly delighted at having put the game to bed.
Defoe should have had a hat-trick in the dying minutes when he was picked out by Andros Townsend, but he volleyed way over.
Reading were determined to score before the final whistle, however, and they almost grabbed one when Le Fondre's shot was cleared off the line by William Gallas.
And they did get themselves on the scoreboard in the dying seconds when Le Fondre clipped a wonderful ball to the back post where substitute Robson-Kanu tapped home from close range.
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