Images from the aftermath of the tornado showed several crumpled vehicles resting against walls and roofs as shellshocked inhabitants of the town of 136,000 struggled to make sense of the devastation.
The tornado came as ferocious weather battered swathes of Mexico and the southern United States, where rescuers hunted for 12 people missing in flash floods across Texas and Oklahoma that left three people dead.
In Mexico, national civil protection coordinator Luis Felipe Puente told Foro TV that "more than 1,000 homes" had been affected by the tornado that swept in at "impressive speed" and lasted only six seconds.
Ciudad Acuna Mayor Evaristo Lenin Perez said a seven-year-old boy was also missing following the tornado, as firefighters and civil protection officials rushed to the town to start searching for survivors in the rubble.
Most of the fatalities were people who were out on the street.