Excess liver fat (LF) is associated with low cardiorespiratory fitness (CRF), low physical activity, and a deteriorated cardiometabolic health profile including increased visceral adipose tissue (VAT). Whether the association between LF and CRF is mediated by visceral adiposity is unknown. We studied the contribution of VAT to the relationship between CRF and LF in asymptomatic women and men. The sample included 320 participants (43% women) who underwent LF quantification by magnetic resonance spectroscopy. VAT was measured by magnetic resonance imaging, CRF using maximal cardiorespiratory exercise testing, and moderate-to-vigorous intensity physical activity (MVPA) using a 3-day journal. Mean age was 50.3 ± 8.6 years, waist circumference was 89.3 ± 11.4 cm, and LF content was 4.3 ± 5.7%. LF was inversely correlated with CRF ( < 0.0001), MVPA ( < 0.05) and cardiometabolic health score ( < 0.0001), and positively related with VAT ( < 0.0001) in both sexes. Significantly higher levels of VAT ( < 0.0001) and subcutaneous adipose tissue ( < 0.0001) and a worsening cardiometabolic health score ( < 0.05) and CRF ( = 0.0001) were found across increasing sex-specific tertiles of LF levels. Lower levels of LF ( < 0.01) and VAT ( < 0.0001) and a higher cardiometabolic health score ( < 0.0001) and MVPA ( < 0.05) were noted across increasing sex-specific CRF tertiles. Multivariable regression analyses showed that visceral adiposity explained the majority of the variance in LF in both sexes ( < 0.0001). Finally, serial mediation analyses revealed that VAT but not body fat percentage was a mediator in the relationship between CRF and LF in both sexes. Thus, visceral adiposity appears to be an important mediator in the relationship between CRF and LF, even after controlling for total adiposity.