ZymoGenetics was established in Seattle in 1981 by University of Washington professors Earl Davie and Benjamin Hall, along with University of British Columbia professor Michael Smith. One of the oldest biotechnology/pharmaceutical companies in the U.S., ZymoGenetics was involved in the development of therapeutic proteins. The company was acquired by Novo Nordisk in 1988, and was spun off as a public company in 2000. Bristol-Myers Squibb acquired the company in 2010.

In 1993, ZymoGenetics moved into a decommissioned 1914 Seattle City Light Steam Plant on Lake Union, and completed historic restoration on the iconic building. In 2019, ZymoGenetics closed its offices at the Steam Plant, sold its Bothell manufacturing site to Seattle Genetics, and ceased operations.