Comprehensive detail of the molecular mechanisms that govern heart development is essential for identifying the etiology of congenital heart disease. We used high-throughput quantitative proteomics to measure temporal changes in the cardiac proteome at eight critical stages of murine embryonic heart development. We identified more than 7,300 proteins, assessed global temporal changes in protein expression, identified cardiac protein interaction networks, and linked protein dynamics with molecular pathways. Using this dataset, we identified and defined a function for the mevalonate pathway in the regulation of embryonic cardiomyocyte proliferation and cell signaling. Overall, our proteomic datasets are an invaluable resource for studying molecular events that regulate embryonic heart development and that contribute to congenital heart disease.