Purpose This study aimed to test the hypothesis that common weight-bearing exercises generate higher lower-limb muscle forces but do not increase medial tibiofemoral contact force (MTCF) when compared with walking in people with medial knee osteoarthritis and varus malalignment. Methods Twenty-eight participants 50 yr or older with medial knee osteoarthritis and varus malalignment were recruited from the community. Three-dimensional lower-body motion, ground reaction forces, and surface EMG from 12 lower-limb muscles were acquired during five squat, lunge, single-leg heel raise, and walking trials, performed at self-selected speeds. An EMG-informed neuromusculoskeletal model with subject-specific bone geometry was used to estimate muscle forces (N) and body weight (BW)-normalized MTCF. The peak forces for muscle groups (knee extensors, knee flexors, ankle plantar flexors, and hip abductors) and peak MTCF were compared with walking using a multivariate analysis of variance model. Results There was a significant main effect (P < 0.001). Post hoc tests (mean difference (95% confidence intervals)) showed that, compared with walking, participants generated higher peak knee extensor and flexor forces during squatting (extensor: 902 N (576 to 1227 N), flexor: 192 N (9.39 to 375 N)) and lunging (extensor: 917 N (604 to 1231 N), flexor: 496 N (198 to 794 N)), and lower peak hip abductor force during squatting (-1975 N (-2841 to -1108 N)) and heel raises (-1217 N (-2131 to -303 N)). Compared with walking, MTCF was lower during squatting (-0.79 BW (-1.04 to -0.53 BW)) and heel raises (-0.27 BW (-0.50 to -0.04 BW)). No other significant differences were observed. Conclusions Participants generated higher peak knee flexor and extensor forces during squatting and lunging but did not increase peak MTCF compared with walking. Clinicians can use these findings to reassure themselves and patients that weight-bearing exercises in these positions do not adversely increase forces within the osteoarthritic joint compartment.