Abstract: No-tillage is one of the most important technologies in conservation agriculture. It is also crucial to understand the impact of no-tillage on grain crop yields, in order to promote the no-tillage application for food security. In this study, a meta-analysis was carried out to determine the regional yield and influencing factors of no-tillage on the three major crops in China. The data was collected from the published literature in Chinese (English) between 1995 and 2023. Conventional tillage (plowing, rotary tillage, or harrowing, depth < 18 cm) was taken as a control. Meta-analysis was employed to quantitatively investigate the overall and regional effects of no-tillage on the yield and yield components of three major grain crops (wheat, maize, and rice). Results showed that there was no significant effect of no-tillage on the regional yields of wheat, maize, and rice on the national scale. However, the regional analysis revealed that the no-tillage significantly increased the wheat yield by 4.1% and 2.2% in the Southwest and Northwest, respectively. There was a significant decrease in the maize yield by 2.4%, 2.6%, and 3.5% in the Northeast, Northwest, and Southeast, respectively. The rice yield was reduced by 1.0% in the Southeast. No significant effects were observed on the wheat and maize yields in North China, or on the wheat and rice yield in the rest regions. The yield components showed that the primary yield effect of no-tillage was attributed to the variation in the effective spikes. The influencing factors were examined on the regional crop yield. The mean annual precipitation was the main contributor to the wheat and maize yield, with the contribution rates of 12.7% and 13.6%, respectively. Soil organic carbon (SOC) content was the primary influencing factor (approximately 16.2%) on regional rice yield under no-tillage. The northwest region was characterized by mean annual temperatures <10 °C, annual precipitation <400 mm, and low soil nutrient content (SOC <10 g/kg, and total nitrogen <1 g/kg). Furthermore, no-tillage significantly increased the wheat yield under single and continuous cropping. Low annual precipitation (< 400 mm) promoted the maize yield in the Northwest, while the high soil pH (>8) and single or triple cropping in two years significantly reduced the crop yield. Specifically, the maize yield decreased in the Northeast and Southeast, which were influenced by the low (< 10 °C) and high (> 15 °C) temperatures, respectively. In the Southeast, the rice yield effects were influenced by the high annual precipitation (>800 mm), soil nutrient content (SOC >15 g/kg, and total nitrogen >1.5 g/kg), as well as the nitrogen and potassium fertilizer inputs. No-tillage was combined with the straw returning and scientific fertilization, in order to minimize the negative yield effect or even increase crop yield. The no-tillage technology was required to fully consider the crop types, regional climate, soil fertility, and cropping systems. These findings can provide a scientific basis to promote no-tillage technology in different agricultural regions in China.