Bolivia took advantage of Lionel Messi's four-match ban and compounded Argentina's misery with a 2-0 win in Tuesday's World Cup qualifying clash in La Paz.
Messi was initially named in head coach Edgardo Bauza's line-up on Monday, but a suspension imposed by FIFA on the day of the game - after the captain insulted a match official in last week's victory over Chile - ruled him out of contention.
It proved a huge blow for an already much-depleted Argentina, whose absences included the banned Nicolas Otamendi, Lucas Biglia, Javier Mascherano and Gonzalo Higuain
The visitors never got going at an altitude of 3,600 metres and Bolivia deservedly took the lead in the 31st minute when Facundo Roncaglia's poor marking was capitalised upon by Juan Carlos Arce, who steered a header past Sergio Romero.
Marcelo Martins added a thunderous second for Mauricio Soria's side in the second half with Angel Correa - deputising ahead of Sergio Aguero for the suspended Messi - producing a disappointing display.
Argentina were unable to recover and remain without a win in Bolivia since 2005, while their woeful record without Messi during the campaign now stands at one win in eight matches without their talismanic captain.
Argentina announced their intention to appeal Messi's suspension prior to kick-off, but even if they are successful it is unlikely he will feature in a potentially pivotal qualifier away to Uruguay in October, by which time they could be fifth in the group, leaving Bauza with plenty of time to stew on another disappointing result.
Perhaps buoyed by Messi's absence, Bolivia had by far the better of the opening exchanges.
After Pablo Escobar's control let him down at the back post and Martins steered a header wide, Arce's goal-bound shot from Escobar's cutback was blocked by Mateo Musacchio in the 15th minute.
Raul Castro's skidding 25-yard drive was parried away from the bottom-left corner by Romero as Bolivia piled on the pressure and limited Argentina to ineffectual counter-attacks.
Bauza's side gradually improved and Ever Banega's dipping shot from just outside the box was tipped behind by Carlos Lampe, the goalkeeper then sprinting off his line to deny Angel Di Maria one-on-one moments later.
They proved important saves as Bolivia took the lead when Arce beat Roncaglia to Escobar's lovely delivery and headed past Romero.
1 - No player had more than one touch in the opp. box (1 Pratto, Correa and Di María); 's Pablo Escobar had 5. Attack. March 28, 2017
Argentina lost Ramiro Funes Mori to a knee injury before half-time and 32-year-old Matias Caruzzo, making his first international appearance since 2010, entered an already ramshackle defence.
Bolivia doubled their lead seven minutes after the restart when Martins slammed home unmarked at the back post after Jorge Flores exploited further shoddy defending from Roncaglia.
Bauza responded by sending on Aguero, but Argentina lacked energy as the game continued and a block from Roncaglia was required to keep Martins at bay.
Substitute Marcos Acuna forced Lampe into a save as Bauza's side tried to salvage something from the game, but their grip on an automatic qualifying spot will likely loosen as a result of the defeat.
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