Wnt regulation of muscle development is thought to be mediated by the beta-catenin-TCF/LEF-dependent canonical pathway. Here we demonstrate that beta-catenin, not TCF/LEF, is required for muscle differentiation. We showed that beta-catenin interacts directly with MyoD, a basic helix-loop-helix transcription factor essential for muscle differentiation and enhances its binding to E box elements and transcriptional activity. MyoD-mediated transactivation is inhibited in muscle cells when beta-catenin is deficient or the interaction between MyoD and beta-catenin is disrupted. These results demonstrate that beta-catenin is necessary for MyoD function, identifying MyoD as an effector in the Wnt canonical pathway.