Higuian bagged an impressive hat-trick while Messi, captaining his country for the first time, scored one to give new coach Alejandro Sabella a triumphant start in his first competitive match in charge.
Chile threatened to stage a revival when Matias Fernandez pulled one back but it was not to be as Higuian completed the rout with his third goal just after the hour-mark.
The Madrid striker opened the scoring on eight minutes after club team-mate Angel Di Maria slid in a pass for Higuian to drive the ball past a helpless Claudio Bravo in the Chile goal.
Messi then scored his 18th international goal in his 63rd appearance in the 26th minute when he was released by a fine pass from Higuain before beating Bravo with a low shot from the edge of the box.
Di Maria was again in the thick of the action, this time setting up his side's third goal - crossing to Higuian who converted with a shot on the turn.
Nine minutes later, Fernandez pulled one back for Chile before Messi teed up Higuian for his hat-trick after a poor clearance by Bravo in the 63rd minute.