Most of the streams that ultimately form the Apure originate in the Venezuelan highlands of the Cordillera de Mérida and only some minor affluents of the Sarare River come from the Cordillera Oriental in the Colombian Andes, entering Venezuela at the confluence with the Oirá River which has a very narrow and steep valley and forms the border between the two countries for 41 kilometres (25 mi).

The Oirá River starts in Venezuela and its thalweg forms that border for several kilometres downstream.

The Uribante River is longer than the Sarare and flows from the Táchira-Mérida border, near the town of Pregonero.

From the point where the Uribante joins the Sarare, the Apure flows eastward across the Venezuelan llanos, into the Orinoco.

Because of the flatness of the land its meanders and bayous to the south are mingled with those of the Arauca River creating an extensive area which is flooded annually.