Solute carrier family 11 member a1 gene (Slc11a1) previously known as natural resistance-associated macrophage protein 1 (Nramp1) is a gene of member of family of metal ion-transport protein. The cellular expression is restricted to phagocytic cells. Slc11a1 delivers bivalent metal cations from the cytosol into acidic endosomal and lysosomal compartments where Fenon and Haber-Weiss reaction generates toxic antimicrobial radicals for direct antimicrobial activity against harmful microorganisms. The present study was undertaken with the objective of analyzing Slc11a1 gene to gain insight into the evolutionary proximity and divergence as well as the polymorphism of this gene in ruminants and non-ruminants including the attendant effects of the genetic variants on the function of the Slc11a1 protein. Thirty Slc11a1 gene sequences of 6 mammalian species classified as ruminant (goat, sheep, cattle, Bubalus bubalis and Bubalus carabanensis) and non-ruminant (swine and horse) animals were investigated. The length of the Slc11a1 gene varied from 448-2,357. There was substantial genetic variation and polymorphism in the aligned sequences of Slc11a1 gene within and across species. Functional analysis of non-synonymous mutations in cattle revealed that twenty five of the amino acid substitutions at the peptide binding region could be beneficial, (E36G), (T52A), (N161S) and (V248I) were likely to be beneficial while only (Q312K) was harmful. In horse, two of the amino acid mutations were harmful, two were likely to be harmful, one was undecided, four were likely beneficial and the rest twenty were beneficial. The phylogenetic trees showed some form of proximity and differentiation in Slc11a1 sequences within and across species. The present information on the polymorphism of Slc11a1 gene might be exploited in the search for association with disease resistance in Nigerian livestock species.