Background: At the onset of steady-state, mild-to-moderate-intensity exercise, breathing quickly increases to levels that precisely and efficiently match metabolic demands. The purpose of this study was to investigate whether respiratory muscles could be potential modulators of this exercise ventilatory response, specifically in childhood cancer survivors (CCS), a population at risk for exertional dyspnea and exercise intolerance. Methods: Inspiratory muscle training (IMT) was used to test the hypothesis that changes in diaphragm structure and function would affect the control of breathing during exercise. Healthy, typically developing, non-cancer controls (HTD) were included for comparison and to explore potential, differential training effects in CCS. We recruited 7 CCS and 10 HTD, aged between 6–12 years, to undergo 6 weeks of IMT (5 sets of 6 breaths, 5 days/week, at 75% of maximal inspiratory pressure [MIP]). Diaphragm structure and function were measured via ultrasonography (diaphragm thickness and excursion) and MIP. A steady-state walking protocol with expired gas analysis was used to evaluate the exercise ventilatory response (respiratory frequency [fR], tidal volume [VT], minute ventilation [V̇E], and ventilatory equivalents for O2 uptake and CO2 production). Results: CCS had reduced thickening of the diaphragm. Breathing patterns were also altered in CCS such that VT during steady-state exercise tended to be lower compared to HTD while fR tended to be higher. Diaphragm thickness was inversely related to the exercise ventilatory response in HTD, but not in CCS. Whereas diaphragm excursion was inversely related to the exercise ventilatory response and perceived exertion in CCS, but not in HTD. After IMT, MIP improved in both groups while exercise tolerance (distance on 6-minute walk test) improved in HTD only. In HTD, the exercise ventilatory response was enhanced, accompanied by improved respiratory motor recruitment and gas exchange efficiency. In CCS, the overall response was attenuated but was more optimal compared to baseline. Conclusions: In CCS, the influence of diaphragm structure and function on the control of breathing during exercise was altered compared to HTD. IMT also produced differential effects in CCS. Pulmonary dysfunction was likely the limiting factor, underscoring the need for continued progress on cancer treatment-related side effects.