Sanchez fired Barca ahead early on and Fabregas added a second 10 minutes into the second half but the damage to Puyol means he will miss the La Liga 'Clasico' against Real Madrid at the Nou Camp on Sunday.
The Catalans had Sergio Busquets dismissed two minutes from time but will be more concerned about Puyol, who landed awkwardly after leaping for a ball and was carried off on a stretcher in obvious pain after 78 minutes.
The Spain international was playing his first match since recovering from a knee problem.
"We are waiting for more information but he will certainly miss the 'Clasico'," Barcelona coach Tito Vilanova told reporters.
Barca defender Dani Alves, who was visibly shaken by Puyol's injury during the match, said his team-mates were concerned.
"We are really saddened by the [Puyol] situation," he said.
Barca have six points from two games and although their confidence is high heading into 'El Clasico', they now have problems at the back with Puyol's defensive partner Gerard Pique also sidelined by injury.
ARCHITECT MESSI
Messi was once again the architect of Barcelona's win in Lisbon.
The Argentine sprinted down the left and crossed for Chilean Sanchez to tap home after six minutes.
Benfica also looked dangerous going forward and Brazilian striker Lima could have levelled five minutes later but Victor Valdez saved at his feet when the striker was through on goal.
With centre-back Luisao suspended, the home side's defence looked wobbly with Artur denying Messi with a reflex save and then the lively Sanchez blasted over the bar with only the keeper to beat.
"There is only one ball and when they have the ball for three quarters of the match it is very hard," said Benfica playmaker Pablo Aimar, who Messi has said was his childhood idol.
Barca doubled their lead after the break when Messi cut in from the right and with a trademark dash left several defenders trailing. He then slid a perfect ball through to Fabregas who coolly slotted in.
"They are, in my opinion, the best in the world, always get more than 70 percent of possession and boss around every opponent," said Benfica coach Jorge Jesus
Celtic beat Spartak Moscow 3-2 in the earlier kickoff in Russia and are second in Group G, with four points after two matches.
