Ramo Grande is a local cattle breed raised in the archipelago of Azores, with a small and dispersed census, where inbreeding control is of utmost importance. A single nucleotide polymorphism (SNP) Beadchip array was used to assess inbreeding, by analysis of genomic regions harboring contiguous homozygous genotypes named runs of homozygosity (ROH), and to estimate past effective population size by analysis of linkage disequilibrium (LD). Genetic markers associated with production traits were also investigated, exploiting the unique genetic and adaptation features of this breed. A total of 639 ROH with length >4 Mb were identified, with mean length of 14.96 Mb. The mean genomic inbreeding was 0.09, and long segments of ROH were common, indicating recent inbred matings. The LD pattern indicates a large effective population size, suggesting the inflow of exotic germplasm in the past. The genome-wide association study identified novel markers significantly affecting longevity, age at first calving and direct genetic effects on calf weight. These results provide the first evidence of the association of longevity with genes related with DNA recognition and repair, and the association of age at first calving with aquaporin proteins, which are known to have a crucial role in reproduction.