Alcohol has many effects on brain function and human behavior, inducing anxiety and sedation, motor incoordination, vomiting, hypnosis, and ultimately unconsciousness. Motor function, in particular, is affected by acute and chronic exposure to alcohol, as several studies have shown. However, the role of the primary motor cortex (M1), a major component of sensorimotor integration, in alcohol-induced motor injury is still unclear. For mouse model of acute alcohol exposure, we intraperitoneally injected alcohol in a single high dose (3 g/kg) and observed the effects of alcohol exposure on neuronal c-Fos expression in mouse brains and behavioral changes in mice. We found significantly decreased locomotion coupled with significantly increased neuronal activation selectively in M1 24 h after injection of alcohol, but anxiety level was not affected. Our findings contribute to the understanding of the association between M1 function and alcohol and open a possible path for early intervention in the treatment of alcohol use symptoms.