Ubiquitin-conjugating enzymes E2 (UBE2) have been reported in the microenvironment of various malignant tumors, but their correlation with ovarian cancer (OC) remains elusive. This study aimed to systematically analyze the expression patterns, prognostic value, genetic variation, and biological functions of 12 members of the gene family in OC through the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, cBioPortal, and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases, respectively. We found that the mRNA levels of , , , and were significantly upregulated in OC compared with those in normal ovarian tissue. In patients with serous ovarian cancer (SOC), , , , , , and upregulation were associated with poor overall survival. Moreover, , , , and upregulation and downregulation were associated with poor progression-free survival. exhibited a strong correlation with OC and was thus further examined. We found that has a high diagnostic accuracy (area under the receiver operating characteristic curve = 0.969) in epithelial ovarian cancer (EOC). Immunohistochemical assays and the Gene Expression Omnibus (GEO) database revealed that was significantly upregulated in EOC compared with that in borderline tumors, benign tumors, and normal ovarian tissues, and its high expression was associated with poor prognosis. The Cox model showed that upregulation was an independent risk factor affecting the prognosis of EOC and SOC. Furthermore, was associated with specific immune cells and was mainly involved in cell cycle-related events. Genomic analysis showed that and mutations were associated with expression. Gene copy number amplification and hypomethylation may be responsible for upregulation in OC. In conclusion, family members may play a role in the development of OC. Specifically, could serve as a new prognostic marker and therapeutic target for this disease. (IRB Approval No. 2020PS533K).