State troopers responded to the scene, south of the First Avenue Bridge, just after midnight on Tuesday after receiving a report of a serious crash.
A preliminary investigation found that both cars, a 2003 Nissan 350 and a red 2000 Daewoo Nubira, were heading south on Highway 509 at high speed when the driver of the Nissan lost control and was hit by the Daewoo.
The Nissan rolled over and came to rest in the middle of the highway.
The driver of the Nissan, a 21-year-old Seattle man, was found seriously injured in the crash. He was taken to Harborview Medical Center.
The driver of the Daewoo, a 22-year-old Seattle man, was arrested and booked into King County Jail for investigation of vehicular assault and DUI.
The highway was blocked for five hours during the investigation, reopening at about 5 a.m. Tuesday.