This study investigated the relationship between yield, thousand kernel weight (TKW), and crude protein of soft white winter wheat-club variety (Barbee) and soft white winter wheat common variety (Zvezdana) susceptible to leaf rust and powdery mildew under different cultivation practices. Results revealed divergence in associations between yield, TKW, and crude protein loss of winter wheat varieties susceptible to obligate pathogens. Under the same level of leaf rust infection, N-input limited yield loss of the two varieties but not to the same extent. TKW loss was affected only by variety×cultivation practice and was significantly correlated with yield loss (r = -0.727, = 0.011) and crude protein loss (r = -0.600, = 0.05) only in club winter wheat. We suspected that Ninput affects the difference in the relationship between yield and TKW loss among varieties. Crude protein and yield loss had a low association (R = 18%, = 0.05). Finally, this study indicated that more attention should be paid to the determination of pathogen pressure that triggers yield loss. It also pointed out that yield, TKW, and crude protein response to fungicides could differ in susceptible varieties. The contribution of fungicide to yield enhancement was highly associated with the specific reaction of the variety to pathogen infection rather than solely the disease level itself.