Argentina gave a performance which is unlikely to rekindle public interest as they beat Bolivia 3-0 at a half-empty River Plate stadium while Paraguay and Uruguay made home advantage count in 2-1 wins over Ecuador and Chile respectively.
Paraguay's Jose Cardozo and Uruguay striker Javier Chevanton both scored their fourth goals in three qualifiers.
Argentina went top of the single South American group with seven points from three games, though they could lose that place when Brazil -- who have six from two -- face Peru in Lima on Sunday.
Paraguay and Uruguay also have six points, Chile four and Venezuela, Bolivia, Peru and Ecuador three apiece.
Beleagured Colombia coach Francisco Maturana was under pressure even before the defeat against opponents who had only ever previously won one qualifier away from home and who come from a country which prefers baseball to soccer.
By the time the final whistle went in Barranquilla, the crowd were shouting "Get out, get out" and the only question seemed to be whether Maturana would resign before or after Wednesday's meeting with Argentina in the same stadium.
Mexican-based Juan Arango did the damage with a rasping 25-metre left foot drive in the eighth minute. After that, Colombia attacked desperately but could not make the breakthrough.
QUALIFIED DENTIST
"I know that you've got a lot of questions and I haven't got many answers," the 54-year-old -- a qualified dentist who took Colombia to the 1990 and 1994 World Cups -- told reporters.
"It's a difficult moment, this result is a slap in the face for Colombian football."
"Despite the situation... this is a group (of players) which is capable of achieving their goals, with or without me."
Argentina, still treated with suspicion by the public after last year's first round exit at the World Cup, struggled for 57 minutes to break down a packed Bolivian defence before Andres D'Alessandro, Hernan Crespo and Pablo Aimar scored in quick succession.
Aimar brightened up a wet, windy night at the River Plate stadium with a cheeky backheel into the net.
But Argentina's performance, in a niggly game full of flying tackles, was still disjointed and they clearly missed suspended Juan Sebastian Veron in midfield.
Chile, unbeaten in their first two games, took a 21st-minute lead against Uruguay in Montevideo but the "Charruas", who started without Alvaro Recoba because of a hamstring injury, equalised with a stunning free kick from Chevanton.
Halftime substitute Marcelo Romero headed the winner four minutes after the break as Chile goalkeeper Nelson Tapia was slow off his line.
Bayern Munich striker Roque Santa Cruz scored the first and set up the second for Cardozo, who last year broke the Mexican championship scoring record by hitting 36 goals in 25 games, as Paraguay once again proved difficult to beat in Asuncion.
Edison Mendez replied for Ecuador who were happy with their performance, if not the result.
"With each day that passes, I like Ecuador more and more," said their Colombian coach Hernan Dario Gomez, who was Maturana's assistant in 1990 and 1994.