Reactive N in the runoff from paddy fields is considered to be the dominant contributor to the deterioration of river and lake water quality in China. However, there has been little researches on the interaction between N fertilizer rates and N losses via runoff from the paddy water during the summer rice-growing seasons. In the present study, we monitored the rice grain yield, N agronomic efficiency (AE_N), and N losses via runoff from fertilizer N rate-response experiments applied to rice in the Taihu Lake region over 6 years. Total N loss via runoff averaged 19.3 kg ha⁻¹ per rice season, corresponding to 7.1% of fertilizer N input at the regional N rate of 270 kg ha⁻¹. Seasonal cumulative ammonium-N, organic N, and total N losses via runoff were all positively correlated with the fertilizer N rates (n = 1141, P < 0.01). The ammonium-N and calculated organic N were the predominant forms in the paddy water. Reducing fertilizer N decreased the risk of ammonium-N and total N losses via runoff but not nitrate-N (consistently low nitrate). Seasonal changes of fertilizer N losses via runoff contributed to the fluctuant rice yields, and the rice yields responses of lower N rates (<135 kg ha⁻¹) might be more susceptible to the massive fertilizer N losses. Reducing the fertilizer N rates by 10–50% (i.e., 135–243 kg ha⁻¹) sustained the current level of rice yields for any single year. By connecting the runoff N loss, rice yield curves, and varying market prices, the mean socially optimum N rates (221 kg ha⁻¹) were proposed for the aim of profit maximization. For the aim of sustainable intensification, however, using less N rates (<221 kg ha⁻¹) was better at controlling runoff losses, and meanwhile sustaining the rice yield. The 135 kg N ha⁻¹ was thus recommended after multiple comparisons of AE_N, N losses via runoff and net returns among different N treatments. Our findings indicated that continuously reducing N fertilizer without modifying other practices is essential and feasible in Eastern China. Reducing N losses via runoff would greatly increase the benefits of society, economy, and environment in responses to unpredictable events.