Different from the developmental mode of western developed countries, China’s economy has changed from a stage of high-speed growth to a stage of high-quality development, where the people’s growing needs for better lives can be met, embodying this new concept of development. The aim of our study is to evaluate the high-quality development efficiency and total factor productivity (TFP) of regional economies in China, and to explore the characteristics of spatial-temporal pattern evolution and their influencing factors. By using the slacks-based measure of directional distance functions (SBM-DDF) model, based on the undesirable output perspective, the high-quality development efficiency and TFP of regional economies in China, from 2000 to 2018, are evaluated in this paper. The exploratory spatial data analysis (ESDA) and Tobit models are then used to identify the spatial-temporal correlation patterns and influencing factors of high-quality development efficiency and TFP. The key results show the following: (1) from 2001 to 2018, the greatest high-quality development efficiency and TFP belonged to China’s eastern region and the least to its central region. (2) U and inverted-U trend lines show that high-quality development efficiency has significant regional difference in the east–west direction, presenting a significant feature of spatial imbalance. (3) Government, urbanization rate, and marketization level play a positive role in their impact of TFP, whereas financial development, infrastructure, foreign direct investment, and capital labor ratio play a negative one.