An error from Fulham goalkeeper Mark Schwarzer allowed Sandro to open the scoring from 30 yards in the 55th minute, before Defoe found the net from close range to make it 2-0.
The England international then added gloss to the scoreline with his second of the afternoon after being fed by Clint Dempsey.
“Whenever you need strikers, Jermain is there for you,” said Villas-Boas, whose side moved up to fourth place in the Premier League table.
“Sometimes strikers might look distant from the game but when the team sets them up it’s important to have that clinical touch and he just has it.
“He’s having an amazing season with us right now, he’s extremely motivated, playing lots of games and it is good to see him happy.”
Villas-Boas also reserved extra praise for Sandro and winger Aaron Lennon after the game.
“We’ve had a very good week following on from the Lazio draw which was an extremely good result for us and there is so many individuals you want to touch on that have been excellent – Sandro, Lennon, people who’ve given their heart for the team and their setting a new standard this season which is good to see.
“Lennon has been absolutely amazing. Not only has he found the back of the net recently and also his defensive work was extreme and Sandro is such an important player for us.
“It obviously it doesn’t stop here, we need to continue with the same momentum, it is important for the club, the players and the fans.”
Get enhanced odds of 5/1 on Arsenal to win the FA Cup on Saturday with Paddy Power.