Santa Fe's trip to Bolivia proved a good one in Thursday's Copa Libertadores action, as they earned a 3-1 victory against Oriente Petrolero.
Two first-half goals from Carlos Ibarguen set up a comfortable away win to hand Santa Fe a sizeable first-leg advantage.
The 20-year-old scored in the 23rd and 41st minutes to put the Colombian side 2-0 up and in complete control of the tie.
Defender Yerry Mina made it 3-0 after 55 minutes, before Oriente substitute Jose Castillo headed home a scrappy consolation goal to hand the Bolivians slender hope of progression into the group stages.
The winner of the tie will join Cerro Porteno, Cobresal and Corinthians in Group 8.
In Ecuador, one goal was all it took for Independiente del Valle to defeat the visiting Guarani.
The Paraguayans will be relatively hopeful of overturning the one-goal deficit on home turf, while Independiente will be delighted to have avoided the concession of an away goal.
Defender Luis Caicedo scored the winner after 29 minutes.
Guarani goalkeeper Alfredo Aguilar had to produce his best form to keep his side in the tie, dealing with eight shots on target while his team-mates at the other end could muster just one.
Guarani now five games without a win in all competitions, but will hope to bounce back and book their spot in Group 5 alongside Colo Colo, Atletico Mineiro and Melgar.