Avon and Somerset Police were called to the junction of Creswicke Road and Airport Road in Knowle West at about 21:05 GMT on Tuesday after reports a man had been run over.
Officers said the crash involved a car and a pedestrian, aged in his 20s, who died from his injuries.
A 30-year-old man has been arrested on suspicion of causing death by dangerous driving and is police custody.
The road has reopened but a nearby petrol station on Hengrove Way remains sealed off while investigations continue.
A spokesman said: "A full investigation has been launched and one of our priorities is to ensure the victim's next of kin are given all the support they need."
A pedestrian has been run over and killed in Bristol.