Wnt growth factors regulate a variety of developmental processes by altering specific gene expression patterns. In vertebrates β‐catenin acts as transcriptional activator, which is needed to overcome target gene repression by Groucho/TLE proteins, and to permit promoter activation as the final consequence of Wnt signaling. However, the molecular mechanisms of transcriptional activation by β‐catenin are only poorly understood. Here we demonstrate that the closely related acetyltransferases p300 and CBP potentiate β‐catenin‐mediated activation of the siamois promoter, a known Wnt target. β‐catenin and p300 also synergize to stimulate a synthetic reporter gene construct, whereas activation of the cyclin D1 promoter by β‐catenin is refractory to p300 stimulation. Axis formation and activation of the β‐catenin target genes siamois and Xnr‐3 in Xenopus embryos are sensitive to the E1A oncoprotein, a known inhibitor of p300/CBP. The C‐terminus of β‐catenin interacts directly with a region overlapping the CH‐3 domain of p300. p300 could participate in alleviating promoter repression imposed by chromatin structure and in recruiting the basal transcription machinery to promoters of particular Wnt target genes.