John van den Brom's Anderlecht was playing without injured playmaker Matias Suarez and suspended midfielder Sacha Kljestan, who impressed in the draw against PSG two weeks ago before being sent off.
Benfica also had injury troubles, with top scorer Oscar Cardozo sidelined with a back injury.
But the goals flowed at the Constant Vanden Stock Stadium despite the missing stars.
In a scrappy first half, both strikes came from set pieces as Anderlecht and Benfica failed to carve out clear-cut scoring chances from open play.
Anderlecht finally scored its first goal at home in this Champions League campaign when Benfica failed to clear a corner in the 18th minute and the ball fell to 19-year-old center back Mbemba, who controlled it on his chest under pressure from Benfica captain Luisao and shot under goalkeeper Artur.
Benfica equalized in the 34th when Matic headed home a curling free kick from the left by Enzo Perez.
After scoring his first Champions League goal in the first half, Mbemba got on the scoresheet a second time, but at the wrong end, when he deflected a shot into his own net after Nicolas Gaitan had turned sharply away from Guillaume Gillet and shot in the 52nd minute.
Bruno looked to have earned Anderlecht a point in the 77th minute when a quick pass from Anthony Vanden Borre set him free behind the Benfica defense and he turned and shot past Artur from a tight angle.
Mbemba came close to stealing a winner with two minutes to play, but was ruled offside after finding the net.
Instead, it was left to Rodrigo to snatch the win for Benfica just minutes after coming on to replace Perez.
