Importance Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are transformational therapies in the treatment of obesity; yet discontinuation rates are high, and patients experience rapid weight regain after stopping treatment. Few scientific publications have reported patients’ experiences of taking GLP-1 RAs in a variety of health contexts outside its use as treatment for type 2 diabetes. Objective To provide insight into the lived experiences of patients taking GLP-1 RAs to inform optimal long-term weight management treatment. Design, Setting, and Participants This qualitative study used inductive thematic analysis of semistructured video interviews conducted between July 22 and September 10, 2025, with participants from 15 US states. Participants included adults who were taking or had previously taken GLP-1 RAs for any treatment indication, recruited through ResearchMatch and snowball sampling. Main Outcomes and Measures Themes identified through inductive thematic analysis. Results Of 30 participants, 10 self-identified as men, 1 as nonbinary, and 19 as women; their mean (SD) age was 54.0 (8.8) years. A total of 23 participants were using a GLP-1 RA at time of interview, and 7 participants had stopped GLP-1 RA use. Eight key themes were extracted and categorized into 2 overarching domains. The first domain was patient-reported benefits and trade-offs. It comprised the following themes: (1) reduction in food noise, psychological hunger, or appetite; (2) GLP-1 RAs are not a standalone weight loss solution; (3) wide spectrum of adverse effects experienced; and (4) patients prepared to withstand substantial adverse effects and logistical challenges to achieve weight loss. The second domain was social, clinical, and structural context. It comprised the following themes: (5) perceived stigma associated with taking GLP-1 RAs, influenced by primary indication for prescription; (6) information provision and clinical support are essential but highly variable; (7) access challenges and cost can be prohibitive; and (8) value of shared experiences. Conclusions and Relevance In this qualitative study of patient experiences with GLP-1 receptor agonists, participants described GLP-1 RA therapy functioning as a facilitator rather than a replacement for lifestyle change, emphasizing the need for behavioral interventions alongside pharmacotherapy to sustain treatment benefits. Quality of care was highly variable; thus, standardized guidelines for patient education and clinical support could improve expectation management around likely adverse effects and long-term management.