Metastatic ovarian cancer patients who have recurrent disease after multiple lines of prior treatment have dismal prognosis. The Kristen rat sarcoma viral oncogene homologue (KRAS) G12C mutation is very rare in ovarian cancers and no approved KRAS G12C targeted treatment options exist for ovarian cancer. Here we present a case of metastatic ovarian serous adenocarcinoma in a female patient in her late 70s who was heavily pretreated with multiple lines of treatment before, showing an excellent durable response to KRAS G12C inhibitor sotorasib at reduced dose of 240 mg oral daily for over 26 months and ongoing. Our case highlights KRAS G12C as a driver mutation in ovarian cancer patients that is potentially targetable in certain subgroups of patients.