The Brazilian side dominated from start to finish on a chilly evening at a half-empty Lincoln Financial Field, with Esperance managing only two attempts on goal.
Giorgian de Arrascaeta and Luís Araújo scored in each half, securing a win for the Copa Libertadores holders.
The loss puts pressure on Esperance, who need a positive result against Los Angeles FC in their next match to keep their qualification hopes alive.
The North African side are looking to bounce back after being defeated in their return to global competition.
Mokwana surely hopes to start in the next game against Los Angeles FC on June 20.
The Major Soccer League side suffered a loss as well against Chelsea, meaning another defeat for either side will bring their World Cup journey to an end.
