In wheat, a shorter pre-anthesis phase is often associated with increased grain protein content (GPC) but decreased grain yield. Cultivar differences in pre-anthesis development are mainly determined by vernalization requirement, photoperiod sensitivity and earliness per se. This research examines whether cultivar differences in these traits affect GPC, especially whether the three traits can partially explain genotype x environment interactions for GPC. Twenty-four winter wheat and five spring wheat cultivars selected from International Winter Wheat Performance Nursery (IWWPN) trials and 12 winter wheats tested over 2 years in Germany were characterized using the CSM-Cropsim-CERES-Wheat model. The model parameter P1V specifies the cultivar vernalization requirement, P1D the photoperiod response, and P-123 earliness per se. Covariance analyses of the IWWPN dataset indicated that about 7% of variation in GPC was explained by cultivar, with another 7% attributable to interactions of cultivar with region, site and year. P1V, P1D and P-123 all influenced GPC, but their effects varied with region, site and year. For example, for two regions, the effect of P1V on GPC decreased with latitude. Path analyses using the data from Germany confirmed that GPC increased with earlier anthesis, which was influenced by P1D and P-123. Lack of an effect of P1V at this location presumably was due to all cultivars being completely vernalized. The results indicate that efforts to improve GPC could target the three traits to specific populations of environments, which should reduce the large influence of environment on GPC.