Goals from Angel Di Maria and Ever Banega secured a deserved three points for Argentina, who exacted sweet revenge for their defeat to the Chileans in last year’s Copa America final.
Chile substitute Jose Fuenzalida scored an injury time consolation for the holders.
The Argentines will now be firm favorites to progress to the quarter-finals as Group D winners with games against Panama and Bolivia to come.
Injured Argentina captain Messi watched from the substitutes’ bench at Levi’s Stadium after failing to recover in time from a sore back suffered in a friendly win over Honduras last month.
But the Barcelona superstar’s absence was barely noticeable, with Nicolas Gaitan slotting into Argentina’s attack and making an instant impression, hitting the woodwork with a header after only two minutes.
That missed chance set the tone for the early exchanges of an entertaining first half which saw Argentina create the lion’s share of opportunities without managing to find a breakthrough goal.
Manchester United defender Marcos Rojo was the next to test Chile goalkeeper Claudio Bravo, unleashing a dipping shot from 20 yards which the Barcelona stopper comfortably saved in the 17th minute.
Sanchez drew a save from Romero in a bright Chilean start to the second half but it was Argentina who opened the scoring on 51 minutes.
A swift counter-attack saw Banega release Di Maria, whose quick low shot flew past Bravo and into the bottom corner as the Chile goalkeeper struggled to get his body into position.
Eight minutes later it was 2-0, Di Maria turning creator this time with a deft pass to Banega whose low shot took a slight deflection off Isla to deceive Bravo.
The game continued to have an edge with Di Maria and Gary Medel both receiving yellow cards for an off-the-ball scuffle shortly afterwards.
In injury time Fuenzalida grabbed a late consolation with a headed goal from a free-kick but it was too little too late.