The purpose of the study was to investigate the effects of using compound sets during a 12-week lower body resistance training program on muscle strength, endurance, hypertrophy, architecture, and soreness. Thirty-one recreationally active females were randomly assigned to one of three groups: traditional sets, compound sets, or control. The training groups performed Smith Machine squat and leg press at matched intensities, volumes, and cumulative rest per session. During compound sets, the squat was performed immediately prior to the leg press, while 1 min rest separated the exercises during traditional sets. A non-exercise control group did not perform resistance training. One-repetition maximum strength, muscle endurance, muscle thickness, cross-sectional area, pennation angle, training session time, and soreness were compared from pre-to post-training (α level < 0.05). Squat and leg press muscle strength and endurance were significantly increased following compound and traditional sets (P < 0.001). Compound and traditional sets were greater than the control group's post-test 1-RM strength and muscle endurance on squat and leg press (P < 0.05). Cross-sectional area and muscle thickness increased after compound and traditional set training from pre-to post-training (P < 0.05). Neither training group had changes to pennation angle. There were no differences between training time per session, as well as subjective soreness at 12 (P > 0.80), 24 (P > 0.50), or 48 (P > 0.30) h post-workout. In conclusion, compound set training, with equated rest, is a method of resistance training that elicits gains similar to traditional sets in young females.