Police said a man opened fire at Cafe Racer, located at 5828 Roosevelt Way NE, at approximately 11 a.m.
Two men were pronounced dead at the scene, and a woman later died at Harborview Medical Center. Two other men sustained life-threatening injuries and were undergoing emergency surgery on Wednesday afternoon.
The gunman remains at large.
Police released surveillance images of the suspected gunman. He is described as a white man between 30 and 40 years old. He is believed to be 6-foot-1 and of thin build with curly light brown hair and a beard. He was last seen wearing a white and brown plaid shirt and dark pants, and was seen headed north as he ran from the scene.
A witness told KOMO News that moments after shots rang out, "a woman ran down the streets and yelled to get back inside; (she said) there was a man with a gun."
Officers have cordoned off the shooting scene and are searching a wide area for the armed man.
"We are asking folks to be on guard and not to open their doors to anybody they don't know," said Assistant Police Chief Nick Metz. "We're focusing our search in the immediate area, probably a good 10 blocks out. We don't have a good idea of where he may be."
It was not known what prompted the shooting, and no information about the victims has been released.
Nearby Roosevelt High School was initally placed under lockdown as a precaution, but later moved to sheltering in place.
Several other schools were sheltering in place in the wake of the shooting, including Greenlake Elementary School, Eckstein Middle School, Ravenna-Eckstein Community Center and Bryant Elementary School.
"Doors are still locked, but classes can go on as normal inside," said Seattle School District spokesperson Theresa Whipple.
Wednesday's shooting was the latest incident in a string of violence that has plagued the Seattle and led some city leaders to openly question whether police are doing enough.
Twenty people have been killed in Seattle so far this year with only seven arrests made, not counting two cases that were cleared.
A woman was fatally shot in Downtown Seattle during an argument with a man on Wednesday, according to police. The gunman in that shooting remains at large.
Last week a man was fatally shot by a stray bullet while he and his family drove down a street in the city's Central District. Justin Ferrari, 43, a software developer, was killed when a stranger started shooting Thursday afternoon. Police said the gunman's intended target was another person involved in a dispute with the gunman.
Ferrari's death was the second random killing in Seattle in about a month. In late April, a 21-year-old woman who recently moved to Seattle from Albuquerque, N.M., to pursue her dream of becoming a chef died of injuries suffered in an apparently random drive-by shooting near downtown. No arrests have been made in either incident.
Last year, the city saw 20 homicide cases. In 2010, there were 19 cases.
This is a developing news story. More details will be published as they become available.