Purpose Studies are increasingly showing that health related stigma is a barrier to employment, but it is not known how. The aim of this systematic review is to identify, appraise and analyse studies that have directly or indirectly addressed ways in which stigma affects sustainable employment and well-being at work of people with disabilities. Methods Using a multiphase screening process, this review is based on a comprehensive literature search (2000-2019) carried out in six electronic databases: Embase, Web of Science, Medline Ovid, Cochrane CENTRAL, PsycINFO and Google Scholar. Results 7.263 publications were identified; 96 studies were found eligible to be included in the review. 72% of the studies were conducted in North America or Europe. Few studies directly assessed how stigma affects the employment of people with disabilities. Most studies highlighted that attitudes and behaviour of employers formed a barrier to employment, as well as anticipated stigma and self-stigma in people with health problems. However, the findings also showed that the attitudes and behaviour of co-workers, health care professionals, reintegration professionals, customers, and family and friends could act as a barrier to employment although these influences are under-researched. Although many similarities were seen in the relevant findings of studies about both physical and mental disabilities, several nuances were found. Conclusion Stigma hampers sustainable employment and well-being in multiple ways. Whereas the number of publications on this topic is rapidly increasing, the roles of health care professionals, reintegration professionals, co-workers, customers, and family and friends particularly warrant more attention.