Operated on an Embraer 175 jet, the new service, which is scheduled to begin on October 01, will be the only nonstop flight offered between the two cities.
John Kirby, vice president, capacity planning, Alaska Airlines, said, "We are excited to add another connection between the Pacific Northwest and California with our new nonstop service between Spokane and San Diego, one of our key focus cities for growth.
"Alaska continues to emphasise our commitment to continued growth and investment throughout the West Coast."
This year, Alaska will average 46 daily departures to 28 destinations from San Diego, including the most nonstop flights to Mexico and Hawaii.