Chile's interior minister Andres Chadwick said anyone living in a 25-kilometer (15-mile) radius of the volcano had been asked to leave -- a total of more than 2,200 people.
Another 800 people were cleared from homes on Argentina's side of the border, according to local officials.
So far, the volcano has only spewed gas, not ash. But Chadwick said seismic activity indicated that an eruption was possible, prompting authorities to move forward with an evacuation plan.
Chile also issued a red alert for the 2,965-meter (9,700 foot) Copahue last December, but an eruption did not follow.
The June 2011 eruption of Chile's Puyehue volcano periodically disrupted air travel in much of the southern cone of South America, and as far away as Australia, for months.
