Chronic nonspecific low back pain (CLBP) is a common musculoskeletal health issue associated with pain and disability reduced quality of life (QoL). Pain initiates a fear-avoidance cycle, which needs to be broken if rehabilitation is to work. To break this cycle, exercise must be gradual and focused on strengthening the weakened musculature. Recently, periodized resistance training was effectively used as a musculoskeletal rehabilitation for adults with CLBP. The purpose of this study was to determine if the volume of periodized musculoskeletal rehabilitation (PMR) influences strength, pain, disability, and QoL in untrained persons. Subjects (n = 240) were age and sex matched, with attempts made to match on strength and pain, and randomly assigned to groups after baseline testing: (a) 4 days per week (4D; n = 60), (b) 3 days per week (3D; n = 60) (c), 2 days per week (2D; n = 60) training volume or control (C; n = 60) with no training. The PMR program progressively overloaded muscle groups, with mean training volumes of 4D (1,563 repetitions [reps] per week), 3D (1,344 reps per week), and 2D (564 reps per week). Three weeks of familiarization and 13 weeks of PMR were employed. The 4D training volume significantly (p ≤ 0.05) outperformed all other training volumes by weeks 9 and 13. However, all training volumes made significant (p ≤ 0.05) improvements in strength, pain, disability, and QoL across time. The effect sizes (ESs) associated with the group means of the outcome measures ranged from moderate to strong, with the 4D training volume consistently demonstrating the largest ESs. The 4D training volume is most effective at treating CLBP. Periodization cannot only be applied to athlete training but also to the rehabilitation setting.