Atypical chemokine receptors (ACKRs) are a subclass of G protein-coupled receptors characterized by promiscuity of ligand binding and an obvious inability to signal after ligand binding. Although some discoveries regarding this family inHomo sapiensand other species have been reported in some studies, the evolution and function of multiple ACKR in mammals have not yet been clearly understood. We performed an evolutionary analysis ofACKRgenes (ACKR1,ACKR2,ACKR3, andACKR4) in mammals. Ninety-two full-lengthACKRgenes from 27 mammal species were retrieved from the Genbank and Ensemble databases. Phylogenetic analysis showed that there were four well-conserved subfamilies in mammals. Synteny analysis revealed thatACKRgenes formed conserved linkage groups with their adjacent genes across mammalian species, facilitating the identification ofACKRsin as yet unannotated genome datasets. Analysis of the site-specific profiles established by posterior probability revealed the positive-selection sites to be distributed mainly in the ligand binding region of ACKR1. This study highlights the molecular evolution of theACKRgene family in mammals and identifies the critical amino acid residues likely to be relevant to ligand binding. Further experimental verification of these findings may provide valuable information regarding the ACKR’s biochemical and physiological functions.