Evolutionary mechanisms have shaped the genomic architecture of Colombian Creole cattle breeds. The mating and selection processes have impacted several traits, promoting differences within and between populations. Studies of population structure and selection signatures in Colombian Creole breeds are scarce, and need more attention to better understand genetic differentiation, gene flow, and genetic distance. This study aimed to analyze the population structure and identify selection imprints in the Criollo Caqueteño (CAQ) population. It used 127 CAQ animals genotyped with Chip HD 777,000 SNPs. The population structure analyses used discriminant principal component analysis (DAPC), integrated haplotype scoring (iHS), and index-fixing (Fst) methodologies to detect selection signals. We can highlight SNP regions on the genes TMPRSS15, PGAM2, and EGFR, identified by the Fst method. Additionally, the iHS regions for cluster 1 identified candidate genes on BTA 3 (CMPK1 and FOXD2), BTA 11 (RCAN1), and BTA 22 (ARPP21). In group 2, we can highlight the genes on BTA 4 (SLC13A4, BRAF), BTA 9 (ULBP), BTA 14 (CSMD3) and BTA 19 (KRTAP9-2). These candidate genes have been associated with fertility traits, precocity, growth, and environmental and disease resistance, indicating a genetic potential in CAQ animals. All this promotes a better understanding of the diversity and genetic structure in the CAQ population. Based on that, our study can significantly assist the sustainable development and conservation of the breed in the Colombian Amazon.