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The Sardo Negro cattle (SN) is the only zebu cattle breed developed in Mexico. Since its development, the selection could have led to an increase in the homozygosity level in some regions of the genome and made differentiation with other cattle populations. We aimed to identify and characterize selection signatures in SN using medium-density SNP data using four approaches: 1) Runs of homozygosity (ROH) 2) Nucleotide Diversity 3) Tajima's D and 4) the Wright's fixation index (FST). A sample of 555 SN animals genotyped for 65k SNPs was used to obtain ROH segments considered regions under selection. The FST values were estimated by comparing the sample of genotyped SN animals with samples of genotyped animals from the Gir, Brahman, and Ongole breeds. Only one region mapped to 35.78–42.51 Mb on BTA6 was considered a selection signature by the ROH method. This selection signature overlapped with the lowest diversity, negative values of Tajima's D and a diversification region between SN and the other Zebu breeds by FST. We found several candidate genes (LCORL, NCAPG, and SLIT2) related to growth and other economically important productive traits in this common region. Using the FST method, different regions, such as regions on BTA8 (8:93.4–93.9 Mb), BTA11 (11:99.2–99.7), and BTA14 (14: 26.1–26.8) related to growth and milk traits also were defined as candidate selection signatures. The selective signals identified in this study reflected the direction of the selection pressure that primarily involves the increase of live weight traits in the Sardo Negro cattle breeding program. [ABSTRACT FROM AUTHOR]