The England striker was again preferred up front to Emmanuel Adebayor and justified the faith shown in him by Villas-Boas by opening the scoring in 18th minute and completing a convincing win with a fine solo effort in the 74th.
Left winger Gareth Bale scored Spurs' other goal, a scuffed finish in the 71st following good work by Kyle Walker down the right, but it was Defoe who will take all the plaudits after destroying Reading's defense.
"Jermain is showing his abilities, the amount of shots he has on target is amazing," Villas-Boas said. "As the lone striker up front, he is linking well with the colleagues."
A first win of the season at the fourth time of asking lifts Spurs into mid-table and eases the pressure on Villas-Boas as the young Portuguese bids to restore his reputation at the London club following his disastrous eight-month spell at Chelsea.
The only negative at the Madejski Stadium for Spurs was the injury-time goal conceded to Hal Robson-Kanu, ruining the clean sheet of veteran Brad Friedel after the American goalkeeper again started ahead of new signing Hugo Lloris.
But Villas-Boas would otherwise have been delighted with Tottenham's fluidity in midfield which had Reading chasing shadows for much of the game. There was time, too, to give Clint Dempsey a late run-out as substitute for the United States forward's first appearance since signing from Fulham on deadline day.
"It was a well-deserved win," Villas-Boas said. "Everyone performed to their top level and it is a win that will lift us up for the season.
"The most important thing today was the motivation of the players to change the negative results at home."
Reading were also looking to claim a first win of the season after opening with a draw and a loss in their first campaign back in the top flight. But the hosts were up against it from the moment Defoe connected with a cutback from Aaron Lennon to sweep a well-placed finish into the bottom corner.
Defoe, who now has three league goals this season as well as two in internationals with England, missed other good chances either side of the break and also set up Gylfi Sigurdsson for a gilt-edged opportunity that the Iceland midfielder saw cleared off the line in the 32nd.
Bale made the game safe when he met a cross from walker with a right-footed shot that bounced into the ground and looped over Reading goalkeeper Alex McCarthy.
Three minutes later, Defoe dispossessed Kaspars Gorkss on the halfway line, charged past two other defenders on a 40-yard run before slipping a shot past McCarthy.
The goal was welcomed with a fist pump on the sidelines by Villas-Boas, who could finally celebrate three points after throwing away winning positions late on against West Bromwich Albion and Norwich.
"Today was a learning curve for all of us," Reading manager Brian McDermott said. "Spurs is a team full of world-class performers, but we didn't cause enough problems for them.
"I thought we were too submissive and didn't get on the ball enough or in their faces."
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