PM2.5 is a major component of air pollution in China and has a serious threat to public health. It is very important to quantify spatial characteristics of the health effects caused by outdoor PM2.5 exposure. This study analyzed the spatial distribution of PM2.5 concentration (45.9 μg/m3 national average in 2016) and premature mortality attributed to PM2.5 in cities at the prefectural level and above in China in 2016. Using the Global Exposure Mortality Model (GEMM), the total premature mortality in China was estimated to be 1.55 million persons, and the per capita mortality was 11.2 per 10,000 persons in the year 2016, resulting in higher estimates compared to the integrated exposure-response model. We assessed the premature mortality attributed to PM2.5 through common diseases, including ischemic heart disease (IHD), cerebrovascular disease (CEV), chronic obstructive pulmonary disease (COPD), lung cancer (LC), and lower respiratory infections (LRI). The premature mortality due to IHD and CEV accounted for 68.5% of the total mortality, and the per capita mortality (per 10,000 persons) for all ages due to IHD was 3.86, the highest among diseases. For the spatial distribution of disease-specific premature mortality, the top two highest absolute numbers of premature mortality associated with IHD, CEV, LC, and LRI, respectively, were found in Chongqing and Beijing. In 338 cities of China, we have found a significant positive spatial autocorrelation of per capita premature mortality, indicating the necessity of coordinated regional governance for an efficient control of PM2.5.