Monson and irregular pluviometric distributions occur frequently, causing waterlogging, which reduces wheat yield under hypoxic conditions. Key hypoxia-related genes are of paramount importance for breeding waterlogging-tolerant wheat varieties. In this study, two spring wheat genotypes with different waterlogging tolerance levels were used to evaluate S-adenosylmethionine synthase family genes. Using wheat genome information, physicochemical properties of the SAMS gene family were analyzed using bioinformatics methods, and TaSAMS10 was chosen because of its positive waterlogging response. The TaSAMS10 gene was cloned into a binary vector then transformed into Arabidopsis plants, and the waterlogging response was recorded. The cis-acting elements in the promoter region of TaSAMS10 revealed the regulatory elements essential for anaerobic induction. Aerenchyma formation was detected in the tolerant genotype but not in the sensitive genotype of wheat. Whereas in TaSAMS10-overexpression Arabidopsis lines, old leaves and roots were exposed to ethylene accumulation, early flowering, and increased survival rates after 20 days of waterlogging treatment. Taken together, the two strategies “escape” and “tolerance” were combined by TaSAMS10 to resist waterlogging stress.