Musculoskeletal injuries occur frequently after road traffic crashes (RTCs), and the effect on work participation is not fully understood. The primary aim of this review was to determine the impact of sustaining a musculoskeletal injury during an RTC on the rate of return to work (RTW), sick leave, and other work outcomes. The secondary aim was to determine factors associated with these work-related outcomes. An electronic search of relevant databases to identify observational studies related to work and employment, RTC, and musculoskeletal injuries was conducted. Where possible, outcome data were pooled by follow-up period to answer the primary aim. Fifty-three studies were included in this review, of which 28 were included in meta-analyses. The pooled rate of RTW was 70% at 1 month, 67% at 3 months, 76% at 6 months, 83% at 12 months, and 70% at 24 months. Twenty-seven percent of participants took some sick leave by one month follow-up, 13% by 3 months, 23% by 6 months, 36% by 12 months, and 22% by 24 months. Most of the factors identified as associated with work outcomes were health-related, with some evidence also for sociodemographic factors. While 70% of people with RTC-related musculoskeletal injury RTW shortly after accident, many still have not RTW two years later.