The rise in usage of and access to new technologies in recent years has led to a growth in digital health behavior change interventions. As the shift to digital platforms continues to grow, it is increasingly important to consider how the field of information architecture (IA) can inform the development of digital health interventions. IA is the way in which digital content is organized and displayed, which strongly impacts users' ability to find and use content. While many information architecture best practices exist, there is a lack of empirical evidence on the role it plays in influencing behavior change and health outcomes. Our aim was to conduct a systematic review synthesizing the existing literature on website information architecture and its effect on health outcomes, behavioral outcomes, and website engagement. To identify all existing information architecture and health behavior literature, we searched articles published in English in the following databases (no date restrictions imposed): ACM Digital Library, CINAHL, Cochrane Library, Google Scholar, Ebsco, and PubMed. The search terms used included information terms (eg, information architecture, interaction design, persuasive design), behavior terms (eg, health behavior, behavioral intervention, ehealth), and health terms (eg, smoking, physical activity, diabetes). The search results were reviewed to determine if they met the inclusion and exclusion criteria created to identify empirical research that studied the effect of IA on health outcomes, behavioral outcomes, or website engagement. Articles that met inclusion criteria were assessed for study quality. Then, data from the articles were extracted using a priori categories established by 3 reviewers. However, the limited health outcome data gathered from the studies precluded a meta-analysis. The initial literature search yielded 685 results, which was narrowed down to three publications that examined the effect of information architecture on health outcomes, behavioral outcomes, or website engagement. One publication studied the isolated impact of information architecture on outcomes of interest (ie, website use and engagement; health-related knowledge, attitudes, and beliefs; and health behaviors), while the other two publications studied the impact of information architecture, website features (eg, interactivity, email prompts, and forums), and tailored content on these outcomes. The paper that investigated IA exclusively found that a tunnel IA improved site engagement and behavior knowledge, but it decreased users' perceived efficiency. The first study that did not isolate IA found that the enhanced site condition improved site usage but not the amount of content viewed. The second study that did not isolate IA found that a tailored site condition improved site usage, behavior knowledge, and some behavior outcomes. No clear conclusion can be made about the relationship between IA and health outcomes, given limited evidence in the peer-reviewed literature connecting IA to behavioral outcomes and website engagement. Only one study reviewed solely manipulated IA, and we therefore recommend improving the scientific evidence base such that additional empirical studies investigate the impact of IA in isolation. Moreover, information from the gray literature and expert opinion might be identified and added to the evidence base, in order to lay the groundwork for hypothesis generation to improve empirical evidence on information architecture and health and behavior outcomes.