King County Metro spokesman Jeff Switzer said the No. 355 bus was heading along 4th Avenue just past the S. Holgate Street intersection at about 6:15 a.m. when it struck a man.
The circumstances leading up to the accident weren't immediately available.
Officials were not able to provide any information about the victim, who was taken to Harborview Medical Center. The extent of injuries was not immediately known.
The street was closed for about an hour for an investigation, but has now reopened.