Abstract Background: Children treated for cancer are at risk for neuromuscular dysfunction, but data are limited regarding prevalence, longitudinal patterns, and long-term impact. Methods: Longitudinal surveys from 25,583 childhood cancer survivors ≥5 years from diagnosis and 5,044 siblings from the Childhood Cancer Survivor Study were used to estimate the prevalence and cumulative incidence of neuromuscular dysfunction. Multivariable models adjusted for age, sex, race, and ethnicity estimated prevalence ratios (PR) of neuromuscular dysfunction in survivors compared with siblings, and associations with treatments and late health/socioeconomic outcomes. Results: Prevalence of neuromuscular dysfunction was 14.7% in survivors 5 years postdiagnosis versus 1.5% in siblings [PR, 9.9; 95% confidence interval (CI), 7.9–12.4], and highest in survivors of central nervous system (CNS) tumors (PR, 27.6; 95% CI, 22.1–34.6) and sarcomas (PR, 11.5; 95% CI, 9.1–14.5). Cumulative incidence rose to 24.3% in survivors 20 years postdiagnosis (95% CI, 23.8–24.8). Spinal radiotherapy and increasing cranial radiotherapy dose were associated with increased prevalence of neuromuscular dysfunction. Platinum exposure (vs. none) was associated with neuromuscular dysfunction (PR, 1.8; 95% CI, 1.5–2.1), even after excluding survivors with CNS tumors, cranial/spinal radiotherapy, or amputation. Neuromuscular dysfunction was associated with concurrent or later obesity (PR, 1.1; 95% CI, 1.1–1.2), anxiety (PR, 2.5; 95% CI, 2.2–2.9), depression (PR, 2.1; 95% CI, 1.9–2.3), and lower likelihood of graduating college (PR, 0.92; 95% CI, 0.90–0.94) and employment (PR, 0.8; 95% CI, 0.8–0.9). Conclusions: Neuromuscular dysfunction is prevalent in childhood cancer survivors, continues to increase posttherapy, and is associated with adverse health and socioeconomic outcomes. Impact: Interventions are needed to prevent and treat neuromuscular dysfunction, especially in survivors with platinum and radiation exposure.