Delta Air Lines will begin flights between Los Angeles and Seattle from 8 April 2013.
The Atlanta-based carrier will offer three daily flights operated by SkyWest Airlines on Bombardier CRJ900s, it says.
Delta previously ended flights on the route in the third quarter of 2008.
The SkyTeam alliance member announced new flights from Seattle to both Shanghai Pudong and Tokyo Haneda, as well as additional frequencies to New York's John F. Kennedy airport in October.
Alaska Airlines, United Airlines and Virgin America offer nonstop flights between Los Angeles and Seattle, according to Innovata schedules. Southwest Airlines offers one-stop service.