Police say the motorcyclist was heading northbound at around 3:30 p.m. when he hit a guardrail and was tossed from his bike near Seneca Street. He died on the scene.
The northbound lanes of State Route 99 remained closed to traffic while police investigated. Traffic was expected to be impacted for several hours.
Thursday's fatal viaduct crash was the second in an as many days.
Thirty-year-old Nathaniel Hammer was killed Wednesday night when he crashed his motorcycle on the Alaskan Way Viaduct and fell to his death.
Hammer was heading northbound just before 9:30 p.m. when he crashed near First Avenue South, according to police.
It's unclear what caused the crash, but Hammer was thrown from his bike and went over the side of the viaduct, landing on Railroad Avenue.
A witness who was below the viaduct at the time of the crash said the rider's helmet flew off when he went off the road.
He was pronounced dead at the scene.