The purpose of this systematic review was to identify the antecedent factors of workplace injuries in small- and medium-sized enterprises (SMEs). A customized systematic review protocol included the research question, literature search, quality appraisal, data management and extraction, and evidence synthesis. The evidence was evaluated using the Critical Appraisal Skills Programme checklists and the Cochrane Collaboration “Risk of Bias” assessment tools. A total of 1355 articles were identified before duplicate removal. Ten articles were relevant to the study objective. Of these, two articles examined antecedents related to physical injuries, three examined those related to psychological injuries, and four focused on a combination. Antecedent factors included older workers, unsafe acts, unsafe working conditions, accident type and type of work performed, trips and falls, loss in productivity, social isolation, financial stress, and lack of employer support during the return to the workplace. The findings of this systematic review support the need for increased research to identify antecedent factors associated with injury in SMEs. Research should focus on interventions to mitigate injury rates that associate employees with employers, thus promoting collaboration in augmenting health and safety in SMEs.