Although Etoile could be feeling inspired ahead of the second leg after managing an away goal, Esperance put one foot into the semi-finals.
Chamseddine Dhaouadi made Esperance’s intentions clear as early as the second minute when he headed home Khalil Chemmam’s free kick.
But Etoile responded through Ammar Jemal who tapped home a low free kick by Firas Belarbi on 29 minutes, to add fire to the contest.
With the scoreline 1-1 at halftime, victory appeared to be slipping away from Esperance who however went on to notch their first victory against Etoile in Caf inter-club competitions.
It was a night where all goals came in from set-pieces with Algerian forward Mohamed Belaïli cleverly squaring in a freekick for an unmarked Sameh Derbali to hammer home for Esperance's winning goal.
Etoile’s goalkeeper Achraf Krir was partly guilty of spilling Derbali’s shot into the net as wild Esperance celebrations followed.
Two-time African champions Esperance are bidding for a first Caf Champions League title since 2011 and made a stride towards that with the win.
Etoile du Sahel’s away goal could set the return leg to be an explosive one in Sousse next weekend.
Earlier in the day in Luanda, five-time African champions TP Mazembe were held to a goalless draw by Angolan champions Primeiro Agosto who are in the quarter-finals for the first time ever.
Agosto were hunting for a goal to take to the second leg in Lumbumbashi next week.
But Nigerian forward Akinfenwa Ibukun failed to take advantage of a howler by TP Mazembe’s Ivorian goalkeeper Sylvain Gbohouo in the 19th minute.
Mazembe also had some good scoring chances coming their way but some poor finishing let them down for a crucial away goal with Ben Malango and Jackson Muleka coming close to break the deadlock.
Late in the match, substitute Ushindi Kubanza had a goal ruled offside as TP Mazembe thought they had finally buried their hosts.
Agosto travel to Lumbumbashi next weekend knowing that an away goal could sail them through to the semifinals, while TP Mazembe would want to avoid conceding at all costs.