In the day's other clash, goals from Veljko Birmancevic and Jo Inge Berget helped Malmo to a 2-0 victory over visiting Ludogorets Razgrad.
A repeat of the 1988 European Cup final, when PSV beat Benfica on penalties to win their maiden title in Europe's premier club competition, produced an entertaining clash at La Luz stadium.
Rafa Silva gave Benfica a 10th-minute lead when he bundled the ball home from eight metres after Roman Yaremchuk put him through with a clever pass.
Julian Weigl made it 2-0 in the 42nd as he buried the ball into the roof of the net from close range following a goalmouth scramble, with Benfica goalkeeper Odisseas Vlachodimos producing a pair of fine saves at the other end.
PSV were on the front foot in the second half after Cody Gakpo pulled one back for the Dutch side with a sizzling low shot in the 51st minute and only a string of superb stops from Vlachodimos denied them an equaliser.
Ferencvaros took an early lead at Young Boys through Franck Boli, who salvaged the Hungarian side's hopes of advancing when he pulled it back to 3-2 after the home team had turned the match on its head.
After Meschack Elia had levelled for Young Boys, Myrto Uzuni missed a penalty for Ferencvaros, with the incident also producing a straight red card for home defender Silvan Hefti who hauled down Endre Botka.
Ferencvaros had the ball in the back of the net from the rebound, as Uzuni's shot cannoned off the post and ricochetted off goalkeeper Guillaume Faivre's back into the path of Aissa Laidouni, but the goal was ruled out for encroachment.
A swerving Vincent Sierro volley and a fine low shot by Ulisses Garcia gave Young Boys a 3-1 lead before Boli struck with a thunderbolt from 20 metres for the visitors to set up a mouth-watering return leg in Budapest.
Malmo dominated Ludogorets and after Anders Christiansen hit the post early on, Birmancevic fired them ahead with a first-time shot in the 26th minute before Berget slid in to steer home a rebound on the hour.
The return legs will be played next Tuesday, with the other three fixtures set for Wednesday.
Sheriff Tiraspol visit Dinamo Zagreb holding a 3-0 first-leg advantage, Brondby host RB Salzburg aiming to overturn a 2-1 deficit and Shakhtar Donetsk are at home to Monaco after beating them 1-0 in the principality.