Introduction The association between occupational mechanical exposures and chronic low back pain (LBP) has been widely studied, however, few systematic reviews have evaluated the evidence of an association. Furthermore, little is known of the impact of occupational psychosocial exposures on chronic LBP. The aim of this systematic review and meta-analysis is to study the association between occupational mechanical and psychosocial exposures and chronic LBP. Methods The study will be conducted as a systematic review using another systematic review published in 2014 as basis and has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) with registration number CRD42021281996. A systematic literature search will be performed in 6 scientific databases to identified potential relevant studies published after 2014. Studies will systematically be excluded through a screening process performed independently by 2 reviewers. Exposures will include occupational mechanical and psychosocial exposures, and outcome will include chronic LBP (LBP ≥3 months, “degenerative” diseases, and lumbosacral radiculopathy). Study population will include persons in or above working age, and study designs will comprise cohort and case-control studies. The quality of each included study will be methodologically assessed by 2 independent reviewers and level of evidence of an association will be graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system. In meta-analyses, effect sizes will be addressed using random-effect models, sensitivity analyses will explore the robustness of the meta-analysis, and heterogeneity assessed. Discussion This systematic review and meta-analysis will assess the evidence available of the association between occupational mechanical and psychosocial exposures and chronic LBP. The review can provide essential knowledge on the association, exposure-response relationships, thresholds, which may pave the way for political decisions on the occupational environment and the labour market insurance policy.