Argentina, looking strong under new coach Alejandro Sabella, dominated from the start. Higuaian scored in the eighth minute, Messi added his in the 26th. Higuain added his second in the 52nd and completed his hat trick in the 63rd.
Matias Fernandez scored for Chile in the 60th.
Argentina, which was knocked out of the Copa America in the quarterfinals three months ago, looked poised and always threatening under Sabella, who replaced the fired Sergio Batista.
Higuain scored his first on a long, arching pass from his Real Madrid teammate Angel Di Maria.
Messi broke through in the 26th, taking a pass from Higuain and slotting home a shot from 14 meters (yards). It was Messi's first goal for Argentina in 17 competitive matches, having not scored in seven World Cup qualifiers, five games at the World Cup and four in the Copa America.
Humberto Suazo had Chile's best chance of the first half in the 43rd, but just shot just wide from close range.
Higuain made it 3-0 in the 52nd, this time take a centering pass from Di Maria and drilling home the shot.
After Fernandez scored in the 60th, Higuain notched his third with Messi setting up the goal with a perfect pass.
Argentina: Mariano Andújar; Pablo Zabaleta, Nicolás Burdisso, Nicolás Otamendi and Marcos Rojo; Jose Sosa, Ever Banega, Rodrigo Braña and Angel Di María; Lionel Messi and Gonzalo Higuaín. Coach: Alejandro Sabella.
Chile: Claudio Bravo; Waldo Ponce, Arturo Vidal and Gonzalo Jara; Mauricio Isla, Carlos Carmona, Jorge Valdivia or Francisco Silva and Jean Beausejour; Matías Fernández; Mauricio Pinilla and Humberto Suazo. Coach: Claudio Borghi.
Referee: Wilmar Roldán Perez (Colombia).