Technical Abstract: Long-term crop rotation effects on crop water use and yield have been investigated in the Central Great Plains since the 1990s. System models are needed to synthesize these long-term results for making management decisions and for transferring localized data to other conditions. The objectives of this study were to calibrate a cropping systems model (RZWQM2 with the DSSAT v4.0 crop modules) for dryland wheat (Triticum aestivum L.), corn (Zea mays L.), and proso millet (Panicum miliaceum L.) production in the wheat–corn–millet (WCM) rotation from 1995 to 2008, and then to evaluate the model from 1992–2008 for two additional rotations, wheat–fallow (WF) and wheat–corn–fallow (WCF) on a Weld silt loam soil under no-till conditions. Measured biomass and grain yield for the above three rotations were simulated reasonably well with root mean squared errors (RMSEs) ranging between 1147 and 2547 kg ha-1 for biomass, and between 280 and 618 kg ha-1 for grain yield. Corresponding index of agreement (d) ranged between 0.70 and 0.95 for biomass, and between 0.87 and 0.97 for grain yield. The validated model was further used to evaluate two additional crop rotations: wheat–millet–fallow (WMF) and wheat–corn–millet–fallow (WCMF) (1993–2008) without prior knowledge of the two rotations. We found that the model simulated the mean and range of yield and biomass of the three crops well. These results demonstrated that RZWQM2 can be used to synthesize long-term crop rotation data and to predict crop rotation effects on crop production under the semiarid conditions of eastern Colorado.