The quake, measuring 7.7 on the Richter scale, hit at 12:43 p.m. local time (15:43 p.m. GMT) on Wednesday, and was centered on Chile's Atacama desert, some 100km (62 miles) north-west of the town of Calama. The area is relatively thinly populated.
Both of the deaths happened in the city of Tocopilla, where many people were also left homeless after the quake destroyed some 100 houses.
Chile's government said it was flying in emergency shelters to the city.
The earthquake, which was so powerful it was felt by people on the other side of the continent, caused massive damage to thousands of homes, as well as cutting off roads and knocking out electricity across northern Chile.
However, the death toll and the damage to property would undoubtedly have been much higher had the earthquake occurred in a more densely-populated area and had it not struck deep underground.
In August, some 500 people perished when an 8.0 magnitude earthquake hit an area near Lima, the capital of neighboring Peru.
