France striker Benzema capitalised after a blunder by the Marseille defence to open the scoring from close range two minutes into the game in Lyon.
Lyon will visit Ligue 1 rivals Lille in early March for a place in the quarter-finals.
The match will be a special occasion for Lyon coach Claude Puel, who joined the seven-times French champions from Lille at the end of last season.
"We controlled the match and it was a logical win," Puel told reporters after a tense game marred by a few ugly scenes.
Lyon played the last 30 minutes with 10 men after Ivory Coast forward Kader Keita was sent off for a second booking but Marseille, who have won the Cup a record 10 times, rarely looked in contention.
The visitors had a great chance to level the tie deep in added time but susbtitute striker Sylvain Wiltord was denied by a fine save from Lyon keeper Hugo Lloris.
Marseille lost striker Bakari Kone after 20 minutes when the Ivory Coast striker had to be substituted after being unintentionally knocked in the head by Lloris's knee. Kone was carried off on a stretcher and taken to hospital for checks.
Benzema nearly doubled Lyon's advantage when he raced into the area and hit the post with angled shot five minutes into the second half.
