In order to validate whether optimizing irrigation and fertilization can improve degraded saline soil and increase wheat production, a 4-year wheat field experiment on saline soil in the Yellow River Delta of China was conducted from October 2013 to June 2017. Eight optimizing treatments including two irrigation applcations of 90 (I90) and 135 (I135) mm/time, four irrigation times: at pre-sowing, wintering, jointing, filling stages, and two fertilizer rates 225 kg N hm −2 -75 P 2 O 5 hm −2 -150with two basal/topdressing ratios 1:1 (A11) and 1:2 (A12) were designed compared with noirrigation and fertilization (CK) and farmer mode (CM). The optimizing treatment combined I135 with F321 and A12 was the optimal practice for wheat production on degraded saline soil in this region. This treatment significantly decreased topsoil salinity on average by 21.97%, increased wheat grain yield, topsoil total N, available P and K, respectively, by an average of 0.74-, 0.75-, 1.13-and 0.78-times, improved water utilization efficiency, water productive efficiency, nitrogen utilization efficiency, phosphorus utilization efficiency, respectively, by average of 1.26-, 8.13-, 0.32-, 0.43-times compared with the CM. These results demonstrate that the optimization of irrigation and fertilization can be extensively applied as a feasible and effective strategy to improve degraded saline soil, maintain soil nutrients, maximize crop yield, and enhance efficiency in other similar degraded saline soil areas of the world.