Both soil fertility and fertilizer N application rate (NA) have important influences on yield and fertilizer N use efficiency (NRE) of wheat. However, it is still unclear about quantitative relationship and relative contribution of their comprehensive effects to the latters. A field experiment was conducted in Changshu of the Taihu Basin. It was designed to have plots different in soil fertility and N application rate for wheat growth, and oriented to explore, how NA and integrated quality index of soil fertility (IFI) affect yield and NRE of the crop. Besides, their quantitative relationships were fitted with the multivariate regression method for analysis of relative contribution rate of the comprehensive effect of NA and IFI to yield and NRE of wheat. Results show that higher NA and IFI helps increase wheat yield, but not NRE of the crop, and that IFI was higher than NA in the effect, and their relative contribution rate was 1.09:1 to wheat yield and 1.32:1 to NRE. The findings of the study suggest that to improve comprehensive quality of the soil may achieve the goal of safety for both grain and ecology, while minimizing N application rate. So to build up soil fertility quality of the farmland is more basic and more important in agricultural production.