Among the dead were three children as the whirlwind damaged an estimated 750 homes in the city across the Rio Grande from Del Rio, Texas, said Jesus Garcia, spokesman for the local state of Coahuila.
The calamity also injured 229 people, all of whom were transported to local hospitals for medical care.
Walls and ceilings collapsed under the force of the whirlwind, which traveled at a speed of some 31 mph (50 km per hour) and blew gusts over 124 mph, the government said, taking the border city unawares in the early hours of Monday.
"We're not used to such destruction," Ciudad Acuna's mayor Evaristo Lenin Perez told local radio. "We don't have records of a single tornado in Acuna, a 110-year-old city."
A spokesman for the National Meteorological Service said it was the strongest tornado for at least 15 years in Mexico. Preliminary findings suggested it registered between a grade EF2 and EF3 on the Enhanced Fujita Scale, the spokesman said.
After the twister had swept through the city, photos showed children climbing past mangled cars that had been swept into their homes, while adults salvaged valuables from the rubble.
"Most of the dead are people who were outside, not people who were inside their homes," Perez said.
Authorities have set up seven refuge points for those whose houses were destroyed, the Coahuila government said.
"We're working on clearing the debris of the destroyed buildings and cars that were displaced," said Francisco Martinez, the deputy minister for Civil Protection in Coahuila.
Coahuila's governor Ruben Moreira arrived this afternoon in Acuna, which had a population of around 134,000 in 2010, and promised authorities will lead the city's recovery.
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