Muscle mass is a commonly cited mediator of the relationship between physical activity (PA) and bone, representing the mechanical forces generated during PA. However, neuromuscular properties (eg, peak force) also account for unique portions of variance in skeletal outcomes. We used serial multiple mediation to explore the intermediary role of muscle mass and force in the relationships between cortical bone and moderate‐to‐vigorous intensity PA (MVPA). In a cross‐sectional sample of young adults (n = 147, 19.7 ± 0.7 years old, 52.4% female) cortical diaphyseal bone was assessed via peripheral quantitative computed tomography at the mid‐tibia. Peak isokinetic torque in knee extension was assessed via Biodex dynamometer. Thigh fat‐free soft tissue (FFST) mass, assessed via dual‐energy X‐ray absorptiometry, represented the muscular aspect of tibial mechanical forces. Habitual MVPA was assessed objectively over 7 days using Actigraph GT3X+ accelerometers. Participants exceeded MVPA guidelines (89.14 ± 27.29 min/day), with males performing 44.5% more vigorous‐intensity activity relative to females (p  < 0.05). Males had greater knee extension torque and thigh FFST mass compared to females (55.3%, and 34.2%, respectively, all p  < 0.05). In combined‐sex models, controlling for tibia length and age, MVPA was associated with strength strain index (pSSI) through two indirect pathways:​ (i) thigh FFST mass (b = 1.11 ± 0.37;​ 95% CI, 0.47 to 1.93), and (i) thigh FFST mass and knee extensor torque in sequence (b = 0.30 ± 0.16;​ 95% CI, 0.09 to 0.73). However, in sex‐specific models MVPA was associated with pSSI indirectly through its relationship with knee extensor torque in males (b = 0.78 ± 0.48;​ 95% CI, 0.04 to 2.02) and thigh FFST mass in females (b = 1.12 ± 0.50;​ 95% CI, 0.37 to 2.46). Bootstrapped CIs confirmed these mediation pathways. The relationship between MVPA and cortical structure appears to be mediated by muscle in young adults, with potential sex‐differences in the muscular pathway. If confirmed, these findings may highlight novel avenues for the promotion of bone strength in young adults.