Higuain put Argentina ahead from Angel di Maria's pass in a counter-attack after seven minutes at the Monumental stadium in Buenos Aires and Messi, whose last goal in a competitive international was against Venezuela in March 2009, netted the second in the 25th.
Higuain chipped in a Di Maria cross from the left seven minutes into the second half and completed his hat-trick when Messi capitalised on a faulty clearance by keeper Claudio Bravo and found the striker with a low pass.
Argentina easily outpaced Chile's vulnerable defence and it took Higuain seven minutes to net a through ball from his Real Madrid team-mate Di Maria.
"It's a great joy to start the qualifiers this way, this new era with a new coach," a cheerful Higuain told reporters referring to Alejandro Sabella, who took charge in August after Argentina's disappointing showing at the Copa America as hosts.
The goal was a timely riposte to criticism from some home fans who felt aggrieved at Messi's failure to emulate his lofty standards at club-level for Barcelona with the national team.
"It's important for Messi to be able to reverse this collective psychosis," said Sabella. "But it's not the most important thing, for if Messi doesn't score, he creates the situations from where goals are scored."
Messi, appointed captain by Sabella on a tour of Asia last month, said: "The team left a good impression and that's what's important. The squad comes before individual happiness."
