A remarkable start saw Marseille given a penalty inside the first minute, as Rasmus Nicolaisen fouled Mason Greenwood in the box.
The latter stepped up and found the bottom corner beyond Kjetil Haug’s reach for his sixth goal of the tournament.
Toulouse responded well, though, as Yann Gboho’s header looped just over, before they found the equaliser minutes later.
Charlie Cresswell’s header from a corner was parried by Geronimo Rulli but only into Gboho’s path, and he made no mistake this time as he tapped home.
Marseille came closest to scoring again before half-time with two brilliant first-time efforts from distance - the first from Arthur Vermeeren as he rattled the crossbar - before Himad Abdelli’s strike was tipped over by Haug.
Toulouse almost turned the tie around early in the second half, as Rulli made a superb double save. First denying Emersonn, then from the resulting corner, the goalkeeper parried away Nicolaisen’s header.
However, it was Marseille who retook the lead with a slice of luck as Geoffrey Kondogbia fed Igor Paixao, who crossed into the box only for the ball to miss everyone and go in off the far post.
The visitors were not disheartened, though, and equalised quickly again from a corner.
Aron Donnum’s wicked delivery found Cresswell, who once more got first contact and this time headed into the net.
Toulouse seemed content with holding on for penalties in the latter stages as Marseille pushed for a winner, with Greenwood in particular leading the charge. He sent a couple of attempts wide of the post, though, and so the tie would be decided by a shootout.
Toulouse went first through Donnum, who slotted calmly past Rulli, before Greenwood levelled proceedings with his second penalty of the night. Gboho then netted again for the visitors, before Pierre-Emerick Aubameyang levelled for Marseille again. Djibril Sidibe kept up the perfect run of penalties before Leonardo Balerdi and Cristian Casseres Jr. both missed.
Nayef Aguerd capitalised with a re-taken spot-kick before Pape Demba Diop made no mistake with the next penalty to apply pressure on Marseille loanee Ethan Nwaneri, who blazed over to send Toulouse through, as the hosts lost out on what would have been a first semi-final appearance since 2015/16.
Flashscore Man of the Match: Charlie Cresswell (Toulouse)
Check out the match summary here.
Nice also through after penalties
Struggling Ligue 1 outfit Nice also progresses to the semi-finals on Wednesday after edging Lorient 6-5 on penalties after their quarter-final ended goalless.
Read a full match report from that match here.
Strasbourg advanced to the final four on Tuesday, while the last quarter-final will be played between Lyon and Lens on Thursday.