Messi scored once while Real Madrid striker Gonzalo Higuain hit a hat-trick to give new coach Alejandro Sabella a triumphant start in his first competitive match in charge. Argentina's Spanish club influence was completed by Angel Di Maria setting up two of the goals for his Real Madrid teammate Higuain.
"It was important to get off on the right foot and we did just that," said Higuain. "I liked a lot of what we did tonight. Now we have to keep this up."
The 1978 and 1986 world champions, rebuilding after a poor Copa America which saw them exit in the quarter-finals, were ahead after eight minutes at Buenos Aires' Estadio Monumental where they haven't lost a FIFA World Cup game for 18 years.
Di Maria slipped in a pass to Higuain who drove the ball high into the net past 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.
Chile, who were without key players Alexis Sanchez and Gary Medel through injury, came close to cutting the deficit in the 42nd minute when Humberto Suazo was unfortunate to see his effort deflected wide by the foot of Pablo Zabaleta.
Di Maria set-up the third for Argentina in the 51st minute when he found Higuain with a smart cross which his Real Madrid teammate converted with a shot on the turn. Nine minutes later Matias Fernandez pulled one back for Chile before Messi teed-up Higuain for a his hat-trick in the 63rd minute after a poor Bravo clearance.