Open vegetable fields in China are a major anthropogenic source of nitrous oxide (N2O) emissions due to excessive nitrogen (N) fertilization. A 4 yr lettuce experiment was conducted to determine the impacts of controlled-release fertilizers (CRFs) and nitrification inhibitors (NIs) on lettuce yield, N2O emissions and net economic benefits. Five treatments included (i) no N fertilizer (CK), (ii) conventional urea at 255 kg N ha–1 based on farmers’ practice (FP), (iii) conventional urea at 204 kg N ha–1 (OPT), (iv) CRF at 204 kg N ha–1 (CU) and (v) CRF (204 kg N ha–1) added with NI (CUNI). No significant differences were found in the lettuce yields among different N fertilization treatments. Compared with FP, the cumulative N2O emissions were significantly decreased by 8.1%, 38.0% and 42.6% under OPT, CU and CUNI, respectively. Meanwhile, the net benefits of OPT, CU and CUNI were improved by USD 281, USD 871 and USD 1024 ha–1 compared to CN, respectively. This study recommends the combined application of CRF and NI at a reduced N rate as the optimal N fertilizer management for the sustainable production of vegetables in China with the lowest environmental risks and the greatest economic benefits.