Chile, the region's dominant side over the past two years with back-to-back Copa America wins, were torn apart as Ecuador produced a rampant display at the Estadio Olimpico Atahualpa.
Goals from Manchester United's Antonio Valencia, Ferencvaros's Cristian Ramirez and Espanyol's Felipe Caicedo secured the points for the hosts.
Chile have never won a competitive fixture in Quito, which is some 9,000 feet (2,743 meters) above sea level. That long record of failure never looked like coming to an end as Ecuador poured forward from the kick off with relentless pressure.
The Manchester United player made no mistake with an emphatic finish that thundered into the bottom corner past Manchester City goalkeeper Claudio Bravo.
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Chile lurched to half-time without conceding another goal but were soon in trouble in the second half.
The win leaves Ecuador second in the overall standings with 16 points from nine games, trailing leaders Uruguay on goal difference.
Chile remain two points outside the qualification places with 11 points from eight games.
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