Alejandro Sabella's side were in fine form and wasted no time in exerting their authority in Chile despite being the away side.
Argentina took the lead on 28 minutes when Fernando Gago found Messi in space in an advanced position.
The Barcelona striker made no mistake with a composed finish to continue his formidable start to the season for club and country.
Higuain then produced a moment of quality to double Argentina's advantage just three minutes later when he fired home from an acute angle.
Chile pressed for a way back into the match for much of the second half but had to settle for a consolation in injury time.
Fernando Gutierrez reduced the deficit but Argentina saw out the final few minutes to make it four wins from their last five World Cup qualifiers.
Sabella's side are now assured of a place at the top of South America's qualifying standings until 2013, leading nearest rivals Ecuador by three points.