Growing evidence has linked cardiorespiratory fitness (CRF) to more conserved white matter (WM) microstructure. Additional research is needed to determine which WM tracts are most strongly related to CRF and if the neuroprotective effects of CRF are age-dependent. Participants were community-dwelling adults (N = 499; ages 20−85) from the open-access Nathan Kline Institute – Rockland Sample (NKI-RS) with CRF (bike test) and diffusion tensor imaging (DTI) data. Mixed-effect modeling tested the interaction between CRF and age on global (main effect across 9 tracts) and local (individual tract effects) WM microstructure. Among older participants (age ≥ 60), CRF was significantly related to whole-brain (z-score slope = 0.11) and local WM microstructure within several tracts (| z-score slope | range = 0.13 – 0.27). Significant interactions with age indicated that the CRF–WM relationship was weaker (z-score slope ≤ 0.11) and more limited (one WM tract) in younger adults. The findings highlight the importance of aerobic exercise to maintain brain health into senescence. CRF may preferentially preserve a collection of anterior and posterior WM connections related to visuomotor function. •Age-related memory complaints in hypertensives are mediated by right hippocampal volume.•Cardiorespiratory fitness (CRF) is linked to preserved white matter (WM) in aging.•The CRFWM relationship was stronger and more widely distributed in older adults.•CRF had a weaker and more limited association to WM in younger adults.•CRF preserves WM anterior and posterior tracts related to visuomotor function.