Inverse dynamics is a standard approach for estimating joint loadings in the lower extremity from kinematic and ground reaction data for use in clinical and research gait studies. Variability in estimating body segment parameters and uncertainty in defining anatomical landmarks have the potential to impact predicted joint loading. This study demonstrates the application of efficient probabilistic methods to quantify the effect of uncertainty in these parameters and landmarks on joint loading in an inverse-dynamics model, and identifies the relative importance of the parameters and landmarks to the predicted joint loading. The inverse-dynamics analysis used a benchmark data set of lower-extremity kinematics and ground reaction data during the stance phase of gait to predict the three-dimensional intersegmental forces and moments. The probabilistic analysis predicted the 1–99 percentile ranges of intersegmental forces and moments at the hip, knee, and ankle. Variabilities, in forces and moments of up to 56% and 156% of the mean values were predicted based on coefficients of variation less than 0.20 for the body segment parameters and standard deviations of for the anatomical landmarks. Sensitivity factors identified the important parameters for the specific joint and component directions. Anatomical landmarks affected moments to a larger extent than body segment parameters. Additionally, for forces, anatomical landmarks had a larger effect than body segment parameters, with the exception of segment masses, which were important to the proximal-distal joint forces. The probabilistic modeling approach predicted the range of possible joint loading, which has implications in gait studies, clinical assessments, and implant design evaluations.