Colorectal cancer (CRC) is one of the leading cancers worldwide, accounting for high morbidity and mortality. The mechanisms governing tumor growth and metastasis in CRC require detailed investigation. The results of the present study indicated that the transcription factor (TF) myocyte enhancer factor 2A (MEF2A) plays a dual role in promoting proliferation and metastasis of CRC by inducing the epithelial-mesenchymal transition (EMT) and activation of WNT/β-catenin signaling. Aberrant expression of MEF2A in CRC clinical specimens was significantly associated with poor prognosis and metastasis. Functionally, MEF2A directly binds to the promoter region to initiate the transcription of ZEB2 and CTNNB1. Simultaneous activation of the expression of EMT-related TFs and Wnt/β-catenin signaling by MEF2A overexpression induced the EMT and increased the frequency of tumor formation and metastasis. The present study identified a new critical oncogene involved in the growth and metastasis of CRC, providing a potential novel therapeutic target for CRC intervention.