Abstract Background Radiation-induced myocardial fibrosis increases heart failure (HF) risk and is associated with a restrictive cardiomyopathy phenotype. The myocardial extracellular volume fraction (ECVF) using contrast-enhanced cardiac magnetic resonance (CMR) quantifies the extent of fibrosis which, in severe cases, results in a noncompliant left ventricle (LV) with an inability to augment exercise stroke volume (SV). The peak exercise oxygen pulse (O₂Pulse), a noninvasive surrogate for exercise SV, may provide mechanistic insight into cardiac reserve. The relationship between LV ECVF and O₂Pulse following thoracic radiotherapy has not been explored. Methods Patients who underwent thoracic radiotherapy for chest malignancies with significant incidental heart dose (≥5 Gray (Gy), ≥10% heart) without a pre-cancer treatment history of HF underwent cardiopulmonary exercise testing to determine O₂Pulse, contrast-enhanced CMR, and N-terminal pro-brain natriuretic peptide (NTproBNP) measurement. Multivariable-analyses were performed to identify factors associated with O₂Pulse normalized for age/gender/anthropometrics. Results Thirty patients (median [IQR] age 63 [57–67] years, 18 [60%] female, 2.0 [0.6–3.8] years post-radiotherapy) were included. The peak VO₂ was 1376 [1057–1552] mL·min^{− 1}, peak HR = 150 [122–164] bpm, resulting in an O₂Pulse of 9.2 [7.5–10.7] mL/beat or 82 (66–96) % of predicted. The ECVF, LV ejection fraction, heart volume receiving ≥10 Gy, and NTproBNP were independently associated with %O₂Pulse (P < .001). Conclusions In patients with prior radiotherapy heart exposure, %-predicted O₂Pulse is inversely associated markers of diffuse fibrosis (ECVF), ventricular wall stress (NTproBNP), radiotherapy heart dose, and positively related to LV function. Increased LV ECVF may reflect a potential etiology of impaired LV SV reserve in patients receiving thoracic radiotherapy for chest malignancies.