The man, who was in his 50s, was hit just before 8 p.m. near the intersection of Martin Luther King Jr. Way South and South Myrtle Street, according to Kyle Moore of the Seattle Fire Department.
Moore said medics "spent a long time trying to save the man" at the scene, but he eventually succumbed to his injuries. A medical examiner will determine the official cause of death.
The victim was the fourth pedestrian struck by a car while crossing a Rainier Valley thoroughfare and the second to have been killed in just one month.
Last week, an 86-year-old woman was struck by a light rail train while she was crossing Martin Luther King Jr. Way South at South Graham Street using a walker, officials said.