Purpose A population-level description and analysis of sepsis-related mortality in China is key to the planning and assessment of interventional strategies. Methods Retrospective analysis of multiple cause of death (MCOD) recorded in the population-based national mortality surveillance system (NMSS) of China. All sepsis-related deaths occurring in 605 disease surveillance points (DSPs) covering 323.8 million population across China were included in our study. Age-standardized mortality and national estimate of sepsis-related deaths were estimated using the census population in 2010 and 2015, respectively. Results In 2015, a total of 1,937,299 deaths occurring in any of the 605 DSPs and standardized sepsis-related mortality rate was 66.7 (95% confidence interval CI 66.4–67.0) deaths per 100,000 population. This produced a national estimate of 1,025,997 sepsis-related deaths. Sepsis-related mortality rates exhibited significant geographic variation. In multilevel analysis, male sex (rate ratio RR 1.582, 95% CI 1.570–1.595), increasing age (RR 1.914 for 5-year group, 95% CI 1.910–1.917), and presence of comorbidity (RR 2.316, 95% CI 2.298–2.335) were independently associated with increased sepsis-related mortality. Higher disposable income (RR 0.717 for the fourth interquartile range vs. the first interquartile range, 95% CI 0.515–0.978) and mean years of education (RR 0.808 for the fourth interquartile range vs. the first interquartile range, 95% CI 0.684–0.955) were negatively associated with sepsis-related mortality. However, population-based hospital doctors were not significantly associated with sepsis-related mortality. Conclusions The standardized sepsis-related mortality rate in China was high and varied according to socioeconomic indices, even though some uncertainty remained.