A suspect was taken into custody within minutes of the incident as he was walking about three blocks away from Central High School, Knoxville television station WATE reported.
The suspect, whose name wasn't released, was being questioned by police. When the suspect was taken into custody, deputies said they recovered a gun.
The victim was identified as Ryan McDonald, 16, who died at the University of Tennessee Medical Center, authorities said.
Police say the shooting occurred in the cafeteria just after 8 a.m. The students involved apparently knew each other and had a previous argument, police said, describing the incident as "not being random," WATE said.
Authorities were alerted to the incident by a sheriff's deputy, whose daughter -- a Central High School student -- called him.