Ahly Midfielder Hussein El Shahat in action during the match against AS FAR. Photo courtesy of Ahly.
The first leg will be played at the Olympic Stadium in Rades, with the return leg scheduled for Cairo on Friday.
Ahly progressed to the quarterfinals as Group A leaders, collecting 10 points, one ahead of Morocco's AS FAR.
Esperance, meanwhile, secured their spot after finishing second in Group D with 9 points, two behind leaders Stade Malien.
Ahly head coach Jess Thorup views the encounter as a highly significant "African derby" between two powerhouse North African sides.
"Ahly against Esperance is an African derby with a rich history between the two teams," Thorup said in his pre-match press conference.
"We fully understand the significance of the game and have prepared well to secure a positive result."
On the other side, newly appointed Esperance coach Patrice Baumel acknowledged the magnitude of the challenge ahead.
"The Ahly clash will be my first big challenge with the team," Baumel remarked after taking charge of the Tunisian giants.
Ahly are chasing a record-extending 13th CAF Champions League title, while Esperance aim for their fifth crown and their first since 2019.
The winner of the two-legged tie will face the victor of the other quarterfinal between South Africa's Mamelodi Sundowns and Stade Malien in the semifinals.
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