This study investigated associations between changes in the total joint moment (TJM) at the knee and changes in cartilage thickness after anterior cruciate ligament reconstruction (ACLR). Seventeen subjects (five males; age: 29.6 ± 7.3 years) with unilateral ACLR underwent gait analysis and magnetic resonance imaging at baseline (2.2 ± 0.3 years post-ACLR) and at long-term follow-up (7.7 ± 0.7 years post-ACLR). Knee loading was assessed using the TJM, and differences in loading were analyzed using repeated measures analysis of variance. Pearson correlation coefficients assessed associations between changes in TJM and changes in (medial-to-lateral) M/L femoral cartilage thickness ratios in the ACLR limb. Bilaterally, there was no significant change in the magnitude of the TJM first peak (TJM1), however, there was a significant increase in the percent contribution of the knee flexion moment (KFM) (p < 0.001) and decrease in the percent contribution of the knee adduction moment (KAM) to TJM1 (p < 0.001). The change in the percent contributions of KFM and KAM to TJM1 were associated with changes in M/L femoral cartilage thickness in the ACLR limb. Specifically, subjects with smaller increases in KFM contribution (R = 0.521, p = 0.032) and smaller decreases in KAM contribution (R = -0.521, p = 0.032) had a reduction in the M/L ratio in the central femoral subregion over the follow-up period, with similar trends in the external femoral subregion. The study results provide new insight into changes in the loading environment at the knee joint prospectively following ACL reconstruction and give evidence that there are modifiable gait metrics that are associated with cartilage changes after ACLR. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1546-1554, 2019.