Karim Aouadhi put the ‘Blood and Gold’ ahead on 41 minutes in Mediterranean resort Sousse and Cameroon-born Yannick Ndjeng struck another goal midway through the second half.
Only Etoile supporters were allowed to watch the match at the Olympic Stadium because of security concerns and there was a pitch invasion after each goal which forced police to use teargas.
The result not only took Esperance to the last four in pursuit of the $1.5 million first prize and a 2012 FIFA Club World Cup place in Japan, it also endangered the chances of former champions Etoile joining them.
Etoile are contesting second place with Sunshine Stars of Nigeria, who won 2-1 to open a three-point advantage and will qualify by winning at home against the Tunisians in the final round.
Esperance have 12 points from four victories and success in Sousse extended to 20 matches an unbeaten run in the premier Pan-African club competition extending back to the 2011 qualifiers.
Sunshine have seven points, Etoile four and the first appearance by Chlef in the group stage has quickly turned into a nightmare with no points after four consecutive losses.
In the probable event of Sunshine losing at Esperance on matchday 5 and Etoile defeating visiting Chlef, the clubs will go into the final round of mini-league fixtures with seven points each.