Foot-and-mouth disease (FMD) is economically the most important viral-induced livestock disease worldwide. In this study, we report the results of a survey of codon usage bias of FMD virus (FMDV) representing all seven serotypes (A, O, C, Asia 1, SAT 1, SAT 2, and SAT 3). Correspondence analysis, a commonly used multivariate statistical approach, was carried out to analyze synonymous codon usage bias. The analysis showed that the overall extent of codon usage bias in FMDV is low. Furthermore, the good correlation between the frequency of G + C at the synonymous third position of sense codons (GC3S) content at silent sites of each sequence and codon usage bias suggested that mutation pressure rather than natural (translational) selection is the most important determinant of the codon bias observed. In addition, other factors, such as the lengths of open reading frame (ORF) and the hydrophobicity of genes also influence the codon usage variation among the genomes of FMDV in a minor way. The result of phylogenetic analyses based on the relative synonymous codon usage (RSCU) values indicated a few obvious phylogenetic incongruities, which suggest that more FMDV genome diversity may exist in nature than is currently indicated. Our work might give some clues to the features of FMDV genome and some evolutionary information of this virus.