Officer Brandon Mendoza, 32, collided head on with the suspect, who had been spotted 30 minutes earlier going southbound in the northbound lines of State Route 51.
The unidentified driver had managed to evade police, who received multiple 911 calls about his erratic behavior. Highway patrol officers made multiple attempts to intercept him, but were unsuccessful.
The suspect eventually drove southbound on US 60 in Tempe, Ariz., when he crashed into the officer.
The wrong-way driver was pronounced dead at the scene, while Mendoza died later at the hospital.
"We are saddened beyond words to report that one of our officers was hit and killed this morning by a wrong way driver," Mesa Police spokesman Tony Landato said in a statement. "The officer had completed their shift and was on their way home."
Mesa Police Chief Frank Milstead described Mendoza as an "iconic" member of his department.