Abstract The Creole cattle from Guadeloupe (GUA) are well adapted to the tropical environment. Its admixed genome likely played an important role in such adaptation. Here, we sought to detect genomic signatures of selection in the GUA genome. For this purpose, we sequenced 23 GUA individuals and combined our data with sequenced genomes of 99 animals representative of European, African and indicine groups. We detect 17,228,983 single nucleotide polymorphisms (SNPs) in the GUA genome, providing the most detailed exploration, to date, of patterns of genetic variation in this breed. We confirm the higher level of African and indicine ancestries, compared to the European ancestry and we highlight the African origin of indicine ancestry in the GUA genome. We identify five strong candidate regions showing an excess of indicine ancestry and consistently supported across the different detection methods. These regions encompass genes with adaptive roles in relation to immunity, thermotolerance and physical activity. We confirmed a previously identified horn-related gene, RXFP2 , as a gene under strong selective pressure in the GUA population likely owing to human-driven (socio-cultural) pressure. Findings from this study provide insight into the genetic mechanisms associated with resilience traits in livestock.