It's the widest travel advisory for Medico in six years, even singling out where tourists should and shouldn't go while visiting the country.
The department advised avoiding travel to Chihuahua, Coahuila and Tamaulipas, which border the U.S, and in the central state of Durango, as well as sections of 10 other states.
It advises caution for traveling in three other border states and many areas of central and western Mexico where drug cartels have been warring.
The advisory said U.S. citizens have been victims of drug violence, including killings, kidnappings and carjackings.
The previous warning in April 2011 recommended avoiding travel in only two states, Tamaulipas and Michoacan, and parts of eight others.
There were also no warnings for the states that are home to Cancun and Cabo San Lucas, two popular tourist destinations for Americans.
The Associated Press contributed to this report.