Despite sitting down in eighth position, Chile will move past their fifth-placed opponents with a win courtesy of their marginally superior goal difference.
Match preview
On the back of winning just two of their opening eight qualification fixtures, Reinaldo Rueda will acknowledge that Colombia are fortunate to still be sitting in the top five.
Colombia have recorded draws against Bolivia and Paraguay since the beginning of the month, failing to take advantage of their share of the spoils with Argentina in June.
Nevertheless, Rueda will be satisfied that his side remain within three points of third-placed Ecuador, a realistic aim behind the two giants of the continent.
On the plus side, three of their draws have been earned from a losing position, but just one clean sheet has been kept in seven matches in all competitions.
Porto attacker Luis Diaz has been Colombia's star of 2021, scoring five goals from his nine appearances on the international stage.
As far as Chile are concerned, head coach Martin Lasarte is under pressure to end a run of four games without finding the back of the net.
The positives will be taken from only losing back-to-back fixtures with Brazil by a 1-0 scoreline, but Lasarte now has just two wins from 10 matches in charge.
Chile still have plenty of time to turn things around during World Cup qualifying, particularly with their next meeting against Brazil or Argentina not scheduled until next year.
However, with the likes of Alexis Sanchez and Eduardo Vargas absent from this fixture, Lasarte will need some of the inexperienced members of his squad to step up for this contest.
Colombia World Cup Qualifying - South America form:
Colombia form (all competitions):
Chile World Cup Qualifying - South America form:
Chile form (all competitions):
Team News
Rueda could potentially hand recalls to Diaz and Radamel Falcao after they both started the last fixture on the substitutes' bench.
Gustavo Cuellar and Alexander Mejia are in contention for a recall in midfield, but Juan Quintero may stay among the replacements.
Diego Valencia is in line to be drafted into the Chile starting lineup as a result of Vargas's suspension.
Pablo Galdames could be provided with an opportunity in midfield before linking up with new club Genoa.
Ben Brereton Diaz is again missing for Chile after Blackburn Rovers prevented the forward from travelling to South America due to coronavirus travel restrictions.
Colombia possible starting lineup:
Ospina; Medina, Sanchez, Murillo, Tesillo; Cuadrado, Barrios, Uribe, Diaz; Borre, Falcao
Chile possible starting lineup:
Bravo; Diaz, Roco, Medel; Isla, Vidal, Baeza, Galdames, Vegas; Valencia, Meneses
We say: Colombia 2-1 Chile
While draws have been the order of the day for these two teams, we do not expect a stalemate on Wednesday night.
Both nations will push hard for all three points, but we favour Colombia to emerge victorious by the odd goal in three.