Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of neurotoxic chemotherapy with limited treatment options. We examined the association between exercise and CIPN symptoms in patients with post-treatment primary breast cancer. Methods: Using a retrospective design, patients completing a standardized survey assessing exercise exposure, neuropathy symptoms, and pain in a tertiary cancer center survivorship clinic were included. Exercise was assessed using a standardized questionnaire quantified in standardized metabolic equivalent tasks (MET-h/wk). Chi-square tests, Mann-Whitney U-tests, Kendall’s rank correlations, and multivariable logistic regressions adjusting for important clinical covariates examined the relationship between exercise and CIPN and whether this differed as a function of chemotherapy regimen (taxane vs. non-taxane based therapy). Results: A total of 5,444 patients with primary breast cancer previously treated with adjuvant chemotherapy (median age 62 years (IQR: 55, 71); median of 4.7 years post chemotherapy completion (IQR: 3.3, 7.6)) were identified. The overall prevalence of CIPN was 34% (95% CI: 33%, 36%); 33% (95% CI: 31%, 34%) for non-taxane and 37% (95% CI: 35%, 39%) for taxane based chemotherapy. The prevalence of CIPN was 28% (95% CI: 26%, 30%) among exercisers (≥5 days of moderate or ≥3 days of strenuous exercise per week) and 38% (95% CI: 37%, 40%) among non-exercisers (difference 11%; 95% CI: 8%, 13%; p < 0.001). Associations appeared dose-dependent. CIPN prevalence was 42% for < 6 MET-h/wk, 33% for 6-20.24 MET-h/wk and 29% for > 20.25 MET-h/wk (p-value < 0.001). Exercise was associated with reduced prevalence of all individual CIPN symptoms (numbness and tingling, pain, interference in daily living). Higher exercise was associated with lower CIPN regardless of chemotherapy regimen. Conclusions: CIPN is persistent several years following chemotherapy cessation in patients with breast cancer but significantly reduced by exercise in a dose-dependent manner.