A suitable crop rotation with optimum fertilizer application can balance the need for high crop yields with minimal environmental risk. This has not yet been achieved in China, and the Chinese Government now requires rotations that include a fallow period with the aim of improving soil quality. As a step towards achieving these aims, a 5-year field experiment was carried out to evaluate the effects of different rates of nitrogen (N) fertilizer in three typical and acceptable crop rotations on grain yield, nitrogen use efficiency (NUE), N balance and economic benefit at Jiangjin, Chongqing, China. The rotations were rice-flooded fallow (RF), rice-wheat (RW) and maize-wheat (MW). Three fertilizer treatments were tested over five years. The RW rotation with reduced fertilizer application had the highest grain yield and generated the highest economic benefit. The MW rotation was not suitable for the region that we studied because high precipitation can cause serious disease problems for the wheat. The RF rotation with reduced fertilizer application proved to be the best system for ensuring food security, increasing economic benefit and reducing environmental risk.