BACKGROUND: Approaches to support the health and well-being of family caregivers of adults with chronic conditions are increasingly important given the key roles caregivers play in helping family members to live in the community. Web-based interventions to support caregivers have the potential to lessen the negative health impacts associated with caregiving and result in improved health outcomes. OBJECTIVE: The primary objective of this systematic review and meta-analysis was to examine the effect of caregiver-focused, Web-based interventions, compared with no or minimal Web-based interventions, on caregiver outcomes. The secondary objective was to assess the effect of different types of Web-based interventions (eg, education, peer and professional psychosocial support, and electronic monitoring of the care recipient), compared with no or minimal Web-based interventions, on caregiver outcomes. METHODS: MEDLINE, EMBASE, CIHAHL, PsychInfo, Cochrane, and AgeLine were searched from January 1995 to April 2017 for relevant randomized controlled trials (RCTs) or controlled clinical trials (CCTs) that compared caregiver-focused, Web-based intervention programs with no or minimal Web-based interventions for caregivers of adults with at least one chronic condition. Studies were included if they involved: adult family or friend caregivers (aged ≥18 years) of adults living in the community with a chronic condition; a caregiver-focused, Web-based intervention of education or psychosocial support or electronic monitoring of the care recipient; and general caregiver outcomes (ie, burden, life satisfaction, self-efficacy or mastery, reaction to problem behavior, self-esteem, strain, and social support). Title and abstract as well as full-text screening were completed in duplicate. Data were extracted by a single reviewer and verified by a second reviewer, and risk of bias assessments were completed accordingly. Where possible, data for these caregiver outcomes were meta-analyzed. RESULTS: The search yielded 7927 unique citations, of which 294 studies were screened at full text. Of those, 14 studies met the inclusion criteria; 12 were RCTs and 1 study was a CCT. One study used an RCT design in 1 country and a CCT design in 2 other countries. The beneficial effects of any Web-based intervention program, compared with no or minimal Web-based intervention, resulted in a mean increase of 0.85 points (95% CI 0.12 to 1.57) for caregiver self-esteem, a mean increase of 0.36 points (95% CI 0.11 to 0.62) for caregiver self-efficacy or mastery, and a mean decrease of 0.32 points (95% CI -0.54 to -0.09) for caregiver strain. However, the results are based on poor-quality studies. CONCLUSIONS: The review found evidence for the positive effects of Web-based intervention programs on self-efficacy, self-esteem, and strain of caregivers of adults living with a chronic condition. Further high-quality research is needed to inform the effectiveness of specific types of Web-based interventions on caregiver outcomes. TRIAL REGISTRATION: PROSPERO CRD42018091715; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=91715 (Archived by WebCite at http://www.webcitation.org/738zAa5F5).