Background: Incidence and mortality of uterine cancer has reported to be declining. However, mortality trends of endometrial serous carcinoma remain unclear at a population level. Methods: We applied SEER to evaluate uterine-serous- carcinoma mortality and relevant deaths of this disease to incident cases. We assessed trends of population mortality based on specific causes and races. Incidence of uterine serous carcinoma were evaluated based on ethics and calendar year. Trends of incidence and incidence-based mortality were evaluated by Joinpoint software. Results: Incidence of uterine serous carcinoma decreased by 1.51% from 2000 through 2017, followed by increase of 16.58% from 2017 through 2019. Mortality of women with uterine serous carcinoma due to uterine serous carcinoma decreased by 4.33% annually from 2000 to 2010, and then decreased at a rate of 1.88% every year from 2010 to 2017, and then sharply declined by 44.69% from 2017 to 2019. Mortality of women with uterine serous carcinoma due to other causes increased by 0.94% annually from 2000 to 2016, and then increased at a high rate of 35.18% every year from 2016 to 2019. Incidence-based mortality of women with uterine serous carcinoma due to other causes increased by 39.03% annually from 2000 to 2004, and then increased at a rate of 2.93% every year from 2004 to 2019. Incidence-based mortality of patients due to other causes showed similar pattern. Patients’ incidence-based mortality due to uterine serous cancer increased at rates of 111.02% and 9.80% annually from 2000 through 2002, from 2002 through 2006 respectively, followed by a decrease of 3.87% annually from 2006 through 2019, and then a gradual increase of 6.55% annually from 2002 through 2005. Incidence of white patients with uterine serous cancer decreased at a rate of 4.42% from 2000 through 2017 and then increased by 21.61% from 2017 through 2019. Incidence of Asians patients presented similar pattern. However, incidence of Black patients increased at a rate of 0.93% from 2000 through 2015 and then sharply increased by 8.49%. Incidence-based mortality of white patients with uterine serous cancer increased at a rate of 105.16% from 2000 through 2002, and then increased by 10.93% from 2002 through 2006, followed by a decrease of 3.40% from 2006 through 2019. Incidence-based mortality of Black patients elevated at a rate of 114.03% from 2000 through 2002, and flatten out, increased by 1.94% from 2002 through 2019. Incidence-based mortality of Asian patients showed similar pattern. Conclusions: Declined incidence-based mortality from 2006 through 2019 may associate with management advances of uterine serous carcinoma. Decreased incidence-based mortality of White patients with uterine serous carcinoma from 2006 through 2019 and increased incidence-based mortality of Black patients and Asian patients with uterine serous carcinoma in same period may related to better management resource of White patients.