ObjectiveThis study aimed to systematically review and summarise the literature on cardiometabolic risk factors, lifestyle health behaviours and mental health status of truck drivers globally to ascertain the scale of these health concerns.DesignSystematic review reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data sourcesPubMed, Scopus, PsycINFO and Web of Science were searched in January 2019 and updated in January 2020, from the date of inception to 16 January 2020.Eligibility criteria for selecting studiesPapers were included if they (1) reported independent data on truck drivers, (2) included quantitative data on outcomes related to cardiometabolic markers of health, mental health and/or health behaviours, (3) were written in English and (4) were published in a peer-reviewed journal. Grey literature was ineligible for this review.Data extraction and synthesisOne reviewer independently extracted data and assessed methodological quality using a checklist based on the National Heart, Lung and Blood Institute Quality Assessment tool. 20% were independently assessed for eligibility and quality by a second reviewer. Due to heterogeneity of the outcomes, results were narratively presented.Results3601 titles and abstracts were screened. Seventy-three studies met the inclusion criteria. Truck driving is associated with enforced sedentarism, long and irregular working hours, lack of healthy foods, social isolation and chronic time pressures. Strong evidence was observed for truck drivers to generally exhibit poor cardiometabolic risk profiles including overweight and obesity, hypertension, hypercholesterolaemia, high blood glucose, poor mental health and cigarette smoking.ConclusionsImproving truck driver health is vital for the longevity of the trucking industry, and for the safety of all road users. The workplace plays a vital role in truck driver health; policies, regulations and procedures are required to address this health crisis.PROSPERO registration numberCRD42019124499.