Santa Fe won comfortably as Atletico Nacional maintained their perfect start to the Copa Libertadores.
Atletico Nacional advanced to the last 16 in the Copa Libertadores with a 4-0 thrashing of Penarol on Tuesday.
Goals from Jonathan Copete, Daniel Bocanegra, Orlando Berrio and Luis Ruiz saw the Colombian outfit to their win in Montevideo.
Copete opened the scoring in the eighth minute, getting on the end of an Alexis Henriquez pass before finishing in a one-on-one.
The visitors had to wait until first-half additional time to double their lead, Bocanegra curling a brilliant 25-yard free-kick into the top corner.
The win was sealed late on as Berrio and Ruiz, the latter with a cheeky chip, struck.
Atletico have won all four of their Group 4 matches to sit eight points clear of Sporting Cristal, with Penarol having earned just one point.
Fellow Colombian side Santa Fe also enjoyed a win, beating Cobresal 3-0 in Group 8 thanks to a Jonathan Gomez brace.
They are level on points with Cerro Porteno atop the group, with Corinthians one behind and Cobresal bottom.
A goal in each half saw Independiente del Valle to a 2-0 victory at home to Melgar in Group 5, while San Lorenzo and Gremio played out a scoreless draw.