Background: The Greek black pig is an autochthonous breed of notable historical, cultural, and agricultural importance. Renowned for its adaptability to extensive farming systems and high-quality meat, it represents a valuable genetic resource within European pig populations. Despite its significance, its genomic landscape remains largely unexplored. To address this, we performed whole-genome sequencing (WGS) of Greek black pigs and wild boars from Greece, aiming to uncover genomic variation, identify functional divergence, and highlight genes and pathways that may be shaped by domestication and environmental adaptation. Materials and Methods: Blood-derived DNA from both populations underwent WGS. Following bioinformatic analysis, missense single-nucleotide polymorphisms (SNPs) and indels were extracted due to their potential functional impact. Per-gene SNP and indel density was calculated. A comparative analysis was conducted to identify genes with unique or shared variants between populations. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed to explore the biological significance of the findings. Results: Distinct sets of missense variants and indels were identified across the two groups. In wild boars, genes such as KRTAP22-1, LCE7A, and TAS2R1 showed high variant density, with functions related to keratin structure and sensory perception. GO and KEGG analyses revealed enrichment in muscle contraction and immune-related pathways. In contrast, Greek black pigs exhibited increased SNP density in genes like TAS2R39, OR5L1Q1, and OR4K2, reflecting alterations in olfactory and taste receptor families. Enriched pathways included calcium signaling and various metabolic processes, potentially linked to domestication and diet. Conclusions: This comparative genomic analysis highlights divergent selection pressures in the studied populations of wild boars and black pigs, offering insights into adaptation, domestication, and the unique genetic profile of the Greek black pig. The results support conservation and sustainable use of local genetic resources.