Soybean mosaic virus (SMV) has threatened the global yield of Leguminosae crops, but the mechanism of its infection, spread, and evolution remains unknown. A systemic analysis of 107 SMV strains was performed to explore the genome-wide codon usage profile and the various factors influencing the codon usage patterns of SMV, which provides insight into its molecular evolution and elucidates its unknown host adaptation pattern. The overall nucleotide composition and correlation analysis revealed that the preferred synonymous codons mostly end with A/U. Clustering by RSCU value of each strain and phylogenetic tree analysis showed that the SMV isolates studied were divided into four clades, with a low overall extent of codon usage bias (CUB) in SMV. According to the ENC, PR2, neutrality plot, and correspondence analysis, natural selection of geographical diversity may play a critical role in the CUB. Higher adaptability was shown in Glycine with SMV and more pressure was received by clade III. These findings could not only provide valuable information about the overall codon usage pattern of the SMV genome, but could also aid in the clarification of the involved mechanisms that dominate the codon usage patterns and genetic evolution of the SMV genome.