Lufthansa will end its flights from Frankfurt to San Jose on 28 October.
The German carrier, which cites "commercial reasons" for the decision, opened the Californian route in June 2016 and has been operating it at five-times-weekly frequency.
Northern California will continue to be served by Lufthansa Group, the Star Alliance member stresses. San Francisco is served from Frankfurt and Munich by Lufthansa and from Zurich by sibling Swiss.
FlightGlobal schedules data indicates that no other airline operates between Frankfurt and San Jose.
The US city's airport is a driving distance of 56km from San Francisco International.