Saccharomyces cerevisiae is an important experimental organism for industrial and scientific research with S. cerevisiae S288C as the first eukaryote genome sequenced. Genome-scale metabolic models (GSMs) are computational tools to explore metabolic engineering requirements. Currently, there are 2 major GSMs of S. cerevisiae S288C, iND750 and iMM904, which raises the question of whether they are consistent to each other. Here, we compare iND750 and iMM904 by examining the fluxomic changes resulting from single reaction knockouts. 40.5% to 50.3% (n = 637) of the reactions are common in both GSMs. Of which, 64 (10.0% of common reactions, or between 4.1% and 5.2% of the total reactions in each GSM) reaction knockouts resulted in significant fluxomic changes. This is significantly lower (t = -15.882, df = 30, p-value = 3.82E-16) from expected using randomization test, suggesting that iND750 and iMM904 are likely to be consistent with each other from the perspective of common reactions.