Background Serious games for health are increasingly being used to address health outcomes in patients with chronic illnesses. These studies vary in their study designs, patient populations, frameworks, outcome variables, and degree of specificity of the serious game intervention. Objective This scoping review aims to clarify the conceptual features of the existing research related to serious games designed to improve cognitive and behavioral outcomes in adults with chronic illness. Methods We applied the Preferred Reporting Items of Systematic Reviews and Meta-Analysis for scoping reviews methodology, including an a priori research question. We searched 4 electronic databases to identify articles published through November 2019. Inclusion criteria encompassed (1) adults 18 years or older; (2) patients with a diagnosis of chronic illness; (3) a serious game intervention; and (4) defined patient outcomes that assess patients’ behavioral, cognitive, or health outcomes. Results Of the 3305 articles identified, 38 were included in the review. We charted and analyzed the theoretical frameworks, key concepts, and outcome variables of these studies with summaries of features across articles. The majority of studies used a randomized controlled trial design (23/38, 61%), included a custom serious game intervention (22/38, 58%), and lacked a theoretical framework (25/38, 66%). Common outcome variables included quality of life (16/38, 42%), mood (15/38, 39%), cognitive function (13/38, 34%), symptoms (12/38, 32%), and physical activity (9/38, 24%). Key differences between studies included whether or not serious games aimed to train versus teach patients, be widely accessible versus tailored interventions, or replace versus complement current treatments. Conclusions This scoping review defines the current landscape of research in serious games for health research targeting behavioral and cognitive outcomes in adults with chronic disease. Studies have addressed a variety of patient populations and diverse patient outcomes. Researchers wanting to build on the current research should integrate theoretical frameworks into the design of the intervention and trial to more clearly articulate the active ingredients and mechanisms of serious games.