Foot-and-mouth disease (FMD) is an extremely contagious viral disease of cloven-hoofed animals. In Pakistan, this disease causes huge losses to economy. However, the reports on its selection and evolutionary pathways are rare. In present study, 336 strains of serotype O (n = 178), A (n = 82) and Asia 1 (n = 76) were downloaded from NCBI database that mainly belonging to Pakistan, along with three vaccinal strains. Phylogenetic analysis (maximum likelihood) showed that lineages Pan Asia II, An Iran-05, and Group VII within serotype O, A and Asia 1 are causing majority of the outbreaks in the Pakistan during recent years. Moreover, only one residue of VP1 region was under positive selection pressure for serotype A (position 141) located in known critical antigenic region but as a whole protein was under negative selection pressure for serotype O, A and Asia 1. Therefore, under mass vaccination campaigns and drastic environmental conditions strains under negative selection has the ability to make escape mutants.