The incorporation of crop straw to cropland is increasingly being recommended due to its ability to improve soil fertility. Controlled-release fertilizer could enhance nitrogen (N) use efficiency and crop grain yield in a rice-wheat rotation cropping system. The effects of controlled-release fertilizer with wheat straw incorporation on rice grain yield and greenhouse gas (GHG) emissions is poorly understood. Four treatments, i.e., chemical fertilizer (CF), chemical fertilizer with straw incorporation (CF + WS), controlled-release urea with straw incorporation (CRU + WS), and no fertilizer (C), were applied to investigate the effects of CRU + WS on rice grain yield, N use efficiency and GHG emissions in multiple rice growing seasons. Relative to CF, rice grain yield from CF + WS decreased by 0.4-2.3% in 2012 and 2013 seasons but increased by 2.3-4.0% in 2014 and 2015 seasons, and significantly enhanced by 9.3% in 2016 season (p < 0.05). No significant difference in N use efficiency was observed between CF and CF + WS in any season, although the trend in that followed the similar pattern as rice grain yield when compared CF + WS with CF. CRU + WS significantly increased rice grain yield by 6.8-18.2% (p < 0.05) and enhanced N use efficiency by 42.0-150.5% (p < 0.05) compared to CF + WS. CH4 emissions from CF + WS and CRU + WS were comparable with each other, which were greatly higher by 156.8-358.6% and by 163.7-364.9% than that from CF, respectively. CF + WS had the potential to reduce N2O emission relative to CF in most rice growing seasons, whereas CRU + WS greatly stimulated N2O emission by 153.0-399.3% and 41.5-319.4% compared to CF and CF + WS, respectively. The GHG emission intensity (GHGI), calculated from greenhouse gases (CH4 and N2O) emissions and rice grain yield from CRU + WS were comparable with that from CF + WS in all rice growing seasons, and they enhanced the GHGI by 165.6-197.7% and by 128.0-253.1% relative to CF, respectively. In conclusion, in the paddy fields with wheat straw incorporation, the application of CRU, rather than conventional CF, could remarkably enhance rice grain yield, improve N use efficiency, but have lithe effect on GHGI due to its stimulation in N2O emission. More efforts are required to mitigate N2O emission when CRU is used in the future.