Farmland drainage is the main contributor to regional non-point source pollution in the rice-wheat rotation area in the lower reaches of the Yangtze River, China, it is of great importance to examine the characteristics of farmland drainage and nitrogen (N) losses for sustainable development of regional agricultural production and ecological environment protection. In the existing studies on drainage and nitrogen losses from rice-wheat rotation fields, nitrogen losses were generally estimated by observing surface runoff and deep percolation with lysimeters or soil column test, which was different from the actual situation that soil moisture and nitrogen entered the drainage system mainly through the lateral flow path. A simulation study on nitrogen losses with field drainage was presented by using the DRAINMOD-NⅡ model; drainage and nitrogen losses from rice-wheat rotation fields under different rainfall conditions were predicted after validating the model with 4-year field monitoring data. The results showed that the predicted average annual nitrogen loss in drainage was 28.4kg/hm2, accounting for 6.0% of the fertilizer application rate; most N losses occurred in the rice growing season with the average value of 25.6kg/hm2. The predicted nitrogen losses in the wheat growing season was only 2.8kg/hm2. When compared with the report values in the existing literature, the total drainage volume was 35.4% higher, and the total nitrogen loss was 44.6% lower. The differences were mainly from wheat growing season, the average reported N losses (31.8kg/hm2) was 11 times of this research. The predicted field drainage and nitrogen losses were significantly correlated to the rainfall pattern (coefficient of determination R2>0.5), the probabilities of the relative increment of the three variables were distributed nearly the same; the predicted nitrogen losses were relatively stable and maintained at 0.8~1.2 times of the average value in normal years with the rainfall return period of less than five years. In the drier or wetter years (i.e., with rainfall return period greater than five years), the predicted nitrogen losses appeared to be more variable. Hence, drainage reduction during the rice growing period through proper control measures was critical to overall reduction of drainage and nitrogen losses from the rice-wheat rotation fields.