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ZBED6, a key transcription factor, plays an important role in skeletal muscle and organ growth. ZBED6 knockout (<i>ZBED6</i>^−/−) leads to the upregulation of <i>IGF2</i> in pig and mice muscle, thereby increasing muscle mass. However, the effects and mechanism of <i>Zbed6</i> single-allele knockout (<i>Zbed6</i>^+/−) on mice muscle remain unknown. Here, we reported that <i>Zbed6</i>^+/− promotes muscle growth by a new potential target gene rather than <i>Igf2</i> in mice muscle. <i>Zbed6</i>^+/− mice showed markedly higher muscle mass (25%) and a markedly higher muscle weight ratio (18%) than wild-type (WT) mice, coinciding with a larger muscle fiber area (28%). Despite a significant increase in muscle growth, <i>Zbed6</i>^+/− mice showed similar <i>Igf2</i> expression with WT mice, indicating that a ZBED6–<i>Igf2</i>-independent regulatory pathway exists in <i>Zbed6</i>^+/− mice muscle. RNA-seq of muscle between the <i>Zbed6</i>^+/− and WT mice revealed two terms related to muscle growth. Overlapping the DEGs and C2C12 Chip-seq data of ZBED6 screened out a potential ZBED6 target gene <i>Barx2</i>, which may regulate muscle growth in <i>Zbed6</i>^+/− mice. These results may open new research directions leading to a better understanding of the integral functions of ZBED6 and provide evidence of <i>Zbed6</i>^+/− promoting muscle growth by regulating <i>Barx2</i> in mice.