A first-half goal from Lucas Pratto was enough for River to overcome Santa Fe 1-0 in Group 4 in Bogota.
Pratto finished clinically in a one-on-one with Robinson Zapata in the 24th minute to give River the win.
Top of the group and undefeated, River's win secured its spot in the knockout stage.
Racing Club is also into the last 16 after edging past Universidad de Chile 1-0 in Group 5.
Alejandro Donatti broke the deadlock in the 81st minute, firing in a 25-yard effort off the post, before Universidad had Lorenzo Reyes sent off.
Racing is three points clear atop the group, having won three of its five matches.
Palmeiras will finish top of Group 8 and recorded a 3-1 win over Alianza Lima, while Libertad is through from Group 3 after beating The Strongest 3-1.