Summary: Superoxide dismutase (SOD) is a crucial metal-containing enzyme that plays a vital role in catalyzing the dismutation of superoxide anions, converting them into molecular oxygen and hydrogen peroxide, essential for enhancing plant stress tolerance. We identified 8 SOD genes (4 CSODs, 2 FSODs, and 2 MSODs) in cassava. Bioinformatics analyses provided insights into chromosomal location, phylogenetic relationships, gene structure, conserved motifs, and gene ontology annotations. MeSOD genes were classified into two groups through phylogenetic analysis, revealing evolutionary connections. Promoters of these genes harbored stress-related cis-elements. Duplication analysis indicated the functional significance of MeCSOD2/MeCSOD4 and MeMSOD1/MeMSOD2. Through qRT-PCR, MeCSOD2 responded to salt stress, MeMSOD2 to drought, and cassava bacterial blight. Silencing MeMSOD2 increased XpmCHN11 virulence, indicating MeMSOD2 is essential for cassava’s defense against XpmCHN11 infection. These findings enhance our understanding of the SOD gene family’s role in cassava and contribute to strategies for stress tolerance improvement.