The visitors will book their place at the World Cup if they avoid defeat on Tuesday as Oscar Tabarez's side looks to climb into the automatic qualifying places.
A 1-0 win over 10-man Ecuador on Friday guaranteed Jose Pekerman's side a place in the AFC-CONMEBOL playoffs at the very worst.
Despite having a one-man advantage for a majority of the game, Colombia was made to work hard for its seventh-consecutive home win and had James Rodriguez to thank for what proved to be a decisive first-half strike.
The result leaves Colombia on the verge of qualifying for its first World Cup since 1998.
Speaking after the game, Peckerman said: "I feel that Colombia won fairly, did important things, took on the role, overcame the difficulties and won well against a very good team.
"Colombia needs to go to the World Cup. We are not there yet, but we've taken a giant step."
Many onlookers will undoubtedly be looking forward to watching two of the biggest names in world football going head-to-head, as Radamel Falcao and Luis Suarez both take to the field.
Despite a ban ruling him out of the start of the new Premier League season, Suarez put in a top performance for Uruguay as the team picked up a vital 2-1 win over Peru in Lima on Friday - although he once again courted controversy.
The Liverpool striker scored from the spot after going over in the penalty area under minimal contact, before his theatrical tumble led to Victor Yotun's red card prior to his emphatic winning strike.
That result left Oscar Tabarez's side with a tightened grip on fifth place, with only two points separating the team from Ecuador in fourth - the final automatic qualifying spot.
Despite suffering a 4-0 defeat in the reverse fixture, history appears to favor Uruguay, which has not lost a competitive home match to Tuesday's opponent since 1973.
Colombia will also be aware that no team has managed to come away from Uruguay with three points since October 2009.