Shannon Lamb, a social science and geography instructor at Delta State University, killed himself after fleeing Greenville police during a traffic stop, said Cleveland Police Chief Charles "Buster" Bingham.
Lamb, 45, was being sought for the Monday killing of Ethan Schmidt, an assistant professor of American history at Delta State, and the earlier shooting of Amy Prentiss in Gautier, a town 300 miles (480 km) away, authorities have said.
Lamb and Prentiss, 41, shared a home. Bingham said it did not appear that the shooting victims knew each other, and police were still investigating the motives for both shootings.
"We don't know why this man did what he did," he said.
The university in Cleveland, Mississippi, canceled events to commemorate its 90th anniversary and instead planned a candlelight vigil to honor Schmidt on Tuesday night.
Schmidt's death followed similar incidents on U.S. college campuses in recent weeks, including at Sacramento City College in California, Texas Southern University and Georgia's Savannah State University.
Law enforcement said when police stopped Lamb's car, he jumped from the vehicle and ran. Officers then heard a gunshot.
While on the run Monday, Lamb had made statements to police that he would not go to jail, the Sun Herald newspaper reported.
Police locked down the Delta State campus and searched buildings on Monday after the reports of gunfire.
Delta State University President William LaForge praised Schmidt, 39, a married father of three children, as a "star" professor.
"I thought the world of him," LaForge said.
LaForge said Lamb was teaching two online courses during the fall semester and did not want a full load, citing medical issues.