This systematic review examines and consolidates existing evidence on stigma associated with the top four non-communicable diseases (NCDs)—cancers, cardiovascular diseases, chronic respiratory diseases, and diabetes—and its impact on the lives of people affected. We conducted a systematic literature search in PubMed, PsycINFO, JSTOR, Science Direct, and Web of Science for original research in English that explored health-related stigma among people living with either of the four NCDs. A three-step integrative synthesis of data was conducted. Twenty-six articles (qualitative = 15; quantitative = 11) were selected, with most (n = 15) related to cancers, followed by diabetes (n = 7), chronic respiratory diseases (n = 3), and cardiovascular diseases (n = 1). Blame, shame, and fear were the main causes of stigma, the origin and nature of which differed according to the disease-specific features. The manifestations (enacted and felt stigma) and consequences (social, behavioral, psychological, and medical) of stigma across NCDs were similar. Inconsistencies existed in the conceptualization of stigma processes. To fill this gap, we developed an NCD-related stigma framework. People living with NCDs can experience stigma, which can negatively impact their health, management of their disease, and quality of life. The new framework can help in improving the understanding of the processes and experiences of stigma related to NCDs.