Messi scored the only goal of the game in the first half in Buenos Aires after Angel Di Maria had been brought down by Chile’s Jose Pedro Fuenzalida.
The Barcelona man calmly sent the ball past Manchester City stopper Claudio Bravo - 269 days after his penalty miss had cost Argentina in the Copa America final shoot-out.
That spot-kick was one of the few moments of note in a gritty first half, although Nicolas Otamendi missed a glorious chance to double the advantage just before the break.
Ever Banega replaced Sergio Aguero on the hour mark, yet Argentina were unable to get a second, with Messi spurning another opportunity from Marcos Rojo’s through-ball.
Chile remained hopeful of grabbing an equaliser and they came desperately close in the dying stages when Alexis Sanchez struck a free-kick against the bar.
Victory sees Argentina move above Chile, Ecuador and Colombia into third place in the South American qualifying group, with five games remaining.
Earlier in the evening, a top-of-the-table clash between Uruguay and Brazil ended in a comfortable 4-1 win for the Selecao, who extended their lead at the top of the qualifying table to seven points.
Without the suspended Luis Suarez, Edinson Cavani led the line and opened the scoring for Uruguay, yet that was as good as it got, as a Paulinho hat-trick, and another international goal for Neymar, ensured the win for the five-time Mundial champions – an eighth consecutive win under coach Tite.
South American World Cup qualifying results:
Colombia 1 – 0 Bolivia
Paraguay 2 – 1 Ecuador
Uruguay 1 – 4 Brazil
Argentina 1 – 0 Chile
Venezuela 2 – 2 Peru