The application of population genetic methods in combination with gene mapping strategies can help to identify genes and mutations selected during the evolution from wild plants to crops and to explore the considerable genetic variation still maintained in natural populations. We genotyped a grapevine germplasm collection of 44 wild (Vitis vinifera subsp. sylvestris) and 48 cultivated (V. vinifera subsp. sativa) accessions at 54 K single-nucleotide polymorphisms (SNPs) to perform a whole-genome comparison of the main population genetic statistics. The analysis of Wright Fixation Index (FST) along the whole genome allowed us to identify several putative "signatures of selection" spanning over two thousand SNPs significantly differentiated between sativa and sylvestris. Many of these genomic regions included genes involved in the adaptation to environmental changes. An overall reduction of nucleotide diversity was observed across the whole genome within sylvestris, supporting a small effective population size of the wild grapevine. Tajima's D resulted positive in both wild and cultivated subgroups, which may indicate an ongoing balancing selection. Association mapping for six domestication-related traits was performed in combination with population genetics, providing further evidence of different perception and response to environmental stresses between sativa and sylvestris.