Cesar Meli played a part in all three of Boca's first-half goals at La Bombonera, while Dani Osvaldo scored both after the break, as the Buenos Aires-based club regained a three-point advantage in Group Five.
Wanderers had joined Boca on six points at the top of Group Five with a win over Palestino on Tuesday but Rodolfo Arruabarrena's side surged to nine with their comprehensive win at home.
Meli opened the scoring in the eighth minute with a drive from the edge of the penalty area, while his cut-back set up Nicolas Lodeiro six minutes later.
In the 37th minute, Meli provided the final pass before Federico Carrizo curled his shot inside the far post.
In the second half, Southampton loanee Osvaldo made it three goals in two Libertadores matches, finishing off Juan Manuel Martinez's centring header in the 69th minute and slotting a penalty with eight minutes remaining.
The result left Zamora bottom of Group Five with the Venezuelan club having yet to pick up a point in three matches.
In Ecuador, Barcelona slumped to their fifth consecutive loss in all competitions despite hitting the front in the first minute against Atletico Nacional.
The Colombian visitors responded with goals to Alejandro Guerra and Luis Ruiz in the second half - the latter in the fifth minute of stoppage time - to register their first win of the continental club competition this season and claim top spot in Group Seven.
Group Six leaders Tigres UANL also won on the road, overcoming San Jose 1-0 in Bolivia, to move four points clear of second-placed Juan Aurich.
