Officers with METRO, the University of Houston, and Texas Southern University are assisting the Houston Police Department as a manhunt begins for the alleged shooter.
Investigators believe the suspect is possibly injured and is running.
Police say the shooting happened in the 3300 block of Reeves Street, which is less than a mile away from both UH and TSU campuses.
Investigators said shots were fired after the suspect and his girlfriend were arguing, and another man intervened.
The suspect allegedly shot the man, in his 20s, several times while he was defending the woman, according to police.
Authorities said the woman was unharmed, but the man was taken to the hospital, where he died.
It is unclear if any college students were involved. Several witnesses who stayed at the scene are being interviewed by homicide detectives.
The shooting comes one week after an unrelated incident when a Texas Southern University Police Department officer working security at an apartment complex opened fire on a suspect who got away.
TSU, UH officers search for suspected shooter after 1 killed, HPD says