Myotonic dystrophy type 1 (DM1) is a multisystem disease that affects every organ system, with muscle weakness and wasting accounting for 60% of patient mortality through respiratory failure. DM1 pathogenesis has been linked to the dysregulation of alternative splicing for thousands of transcripts, which overall display a reversion from adult to fetal splice-patterning. Consequently, this leads to the inappropriate expression of the fetal transcript isoforms in adult tissue, some of which encode proteins that possess altered function, ill-suited to participate in adult cellular processes. However, efforts to link individual splice events to specific disease symptoms has proven difficult due to the widespread nature of splicing dysregulation, and thus the molecular mechanism underlying myopathy remains unknown. Our lab recently demonstrated that the fetal splice isoform of a skeletal muscle calcium channel, Cav1.1 (Cav1.1-e29), with chloride channel myotonia is sufficient to promote severe muscle weakness, impaired respiratory function and reduced survival. Cav1.1-e29 displays a gain-of-function with increased calcium entry upon depolarization. Together, we hypothesize that this exacerbates myopathy in DM1 through alterations in muscle excitability and subsequent calcium toxicity. To understand the role of Cav1.1-e29 in DM1, a splice-mimicking mouse model of Cav1.1-e29 was crossed with the HSALR and Mbnl1 KO models of DM1 that display minimal Cav1.1 mis-splicing and myopathy. The degree of myopathy was assessed by tracking survival, in vitro muscle contraction, in vivo muscle contraction with paired EMG recordings, and histology. We show that when Cav1.1-e29 was forcibly expressed in Mbnl1-/- mice, myopathy is exacerbated with a reduction in lifespan, altered respiratory function, and worsening histopathological features. Overall, this study advances the field by elucidating the role of Cav1.1 mis-splicing in driving DM1 myopathy and provides evidence that blocking Cav1.1 conductance may provide a therapeutic benefit.