Darwin’s finches from the Galápagos are a celebrated study model regarding the processes of natural selection and adaptive evolution. Adaptation to the striking ecological differences throughout Galápagos have led to rapid diversification and speciation in these birds. This has resulted in remarkable diversity in their morphology, specifically the shape and size of the beaks. Long-term field studies in the past have documented that beaks in Darwin’s finches correspond to specific feeding niche they occupy and evolve by natural selection in response to limiting food resources and interspecific competition. We have done extensive genomic characterization of the entire Darwin’s finch radiation by whole-genome sequencing 180 birds that included all currently recognized species. Genome-wide comparisons among species with different beak shapes (blunt and pointed) and beak sizes (large, medium and small) identified candidate genes associated with beak morphology. The strongest association to beak shape was ALX1, a transcription factor involved in craniofacial development. Similarly HMGA2, a transcriptional regulating factor previously linked to human height and body size in other species, showed the strongest association to beak size. Interestingly, both loci were segregating in the medium ground finch, the species with considerable diversity in beak morphology. Genotyping these two loci in additional medium ground finches and comparison with individual measurements of beak shape and size confirmed the association and suggested additive effects of these loci, as heterozygotes showed intermediate beak types compared with the two homozygotes. In addition, HMGA2 loci also had played a critical role in a documented character displacement episode in Darwin’s finches when medium ground finches diverged from their competitor, the large ground finch, during a severe drought. In conclusion, we have provided evidence of two loci with major effects on beak morphology (shape and size), which probably were the most important trait during the adaptive radiation of Darwin’s finches.