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Milk production is an essential economic trait in cattle, and understanding the genetic regulation of this trait can enhance breeding strategies. The discoidin domain receptor 1 (<i>DDR1</i>) gene has been identified as a key candidate gene that influences milk production, and ETS homologous factor (EHF) is recognized as a critical transcription factor that regulates <i>DDR1</i> expression. Codon usage bias, which affects gene expression and protein function, has not been fully explored in cattle. This study aims to examine the codon usage bias of <i>DDR1</i> and EHF transcription factors to understand their roles in dairy production traits. Data from 24 species revealed that both <i>DDR1</i> and EHF predominantly used G/C-ending codons, with the GC3 content averaging 75.49% for <i>DDR1</i> and 61.72% for EHF. Synonymous codon usage analysis identified high-frequency codons for both <i>DDR1</i> and EHF, with 17 codons common to both genes. Correlation analysis indicated a negative relationship between the effective number of codons and codon adaptation index for both <i>DDR1</i> and EHF. Phylogenetic and clustering analyses revealed similar codon usage patterns among closely related species. These findings suggest that EHF plays a crucial role in regulating <i>DDR1</i> expression, offering new insights into genetically regulating milk production in cattle.