Scientific discovery and technological innovation are the ultimate forces that promote socioeconomic development. However, researchers are not certain which factors play a leading role in scientific discovery and technological innovation and what differences in these factors exist between regions. In this study, we selected 286 prefecture-level Chinese cities and developed a coupling model to link them within a comprehensive evaluation framework, then performed multiple linear regression model and geographically weighted regression model to identify the key driving factors for scientific discovery and technological innovation, their contributions to innovation, and their regional differences. We found that marketization (development of a market economy), population density, industrial upgrading, health care, and industrialization most strongly promoted Chinese innovation from 2007 to 2019, whereas the innovation level decreased with increasing environmental pollution. To promote scientific discovery and technological innovation, we should increase marketization, promote market-oriented reform of universities, sustainably increase population density, and upgrade the industrial structure, while simultaneously reducing pollution. These results will provide important guidance for the formulation of China's future science and technology policy, but our method will also help other countries learn how to improve their own science and innovation by learning from China's experience.