Public Safety Commissioner Rusty Fortenberry said the new division is under the control of the Mississippi Bureau of Investigation and will be located at the department's crime laboratory in Batesville.
The unit will accept unsolved cases from Police and Sheriff's Departments across Mississippi.
Only a few states have cold case units, which review unsolved cases that appear to have no active leads.
The Maryland State Police has a comprehensive list of cold case units across the nation. It shows only two other southern states with similar units.
The Texas Department of Public Safety operates a cold case unit under the control of the Texas Rangers, and the Florida Department of Law Enforcement has a cold case committee, according to Maryland State Police.
In Mississippi, local law enforcement agencies traditionally have handled their own cold cases, but officials say the agencies often lack the manpower to stay on the job.
Steve Chancellor, a 30-year law enforcement veteran, is head of the unit.