BACKGROUND: Patients with chronic pain often have limited access to comprehensive care that includes behavioral pain management strategies. Virtual reality (VR) is an immersive technology and emerging digital behavioral pain therapy with analgesic efficacy for acute pain. We found no scientific literature on skills-based VR behavioral programs for chronic pain populations. OBJECTIVE: The primary aim of this study is to evaluate the feasibility of a self-administered VR program that included content and skills informed by evidence-based behavioral treatment for chronic pain. The secondary aim is to determine the preliminary efficacy of the VR program in terms of average pain intensity and pain-related interference with activity, stress, mood, and sleep, and its impact on pain-related cognition and self-efficacy. The tertiary aim was to conduct a randomized controlled trial (RCT) and compare the VR treatment with an audio-only treatment. This comparison isolated the immersive effects of the VR program, thereby informing potential mechanisms of effect. METHODS: We conducted an RCT involving a web-based convenience sample of adults (N=97) aged 18-75 years with self-reported chronic nonmalignant low back pain or fibromyalgia, with an average pain intensity >4 over the past month and chronic pain duration >6 months. Enrolled participants were randomly assigned to 1 of 2 unblinded treatments: (1) VR: a 21-day, skills-based VR program for chronic pain; and (2) audio: an audio-only version of the 21-day VR program. The analytic data set included participants who completed at least 1 of 8 surveys administered during the intervention period: VR (n=39) and audio (n=35). RESULTS: The VR and audio groups launched a total of 1067 and 1048 sessions, respectively. The majority of VR participants (n=19/25, 76%) reported no nausea or motion sickness. High satisfaction ratings were reported for VR (n=24/29, 83%) and audio (n=26/33, 72%). For VR efficacy, symptom improvement over time was found for each pain variable (all P<.001), with results strengthening after 2 weeks. Importantly, significant time×group effects were found in favor of the VR group for average pain intensity (P=.04), pain-related inference with activity (P=.005), sleep (P<.001), mood (P<.001), and stress (P=.003). For pain catastrophizing and pain self-efficacy, we found a significant declining trend for both treatment groups. CONCLUSIONS: High engagement and satisfaction combined with low levels of adverse effects support the feasibility and acceptability of at-home skills-based VR for chronic pain. A significant reduction in pain outcomes over the course of the 21-day treatment both within the VR group and compared with an audio-only version suggests that VR has the potential to provide enhanced treatment and greater improvement across a range of pain outcomes. These findings provide a foundation for future research on VR behavioral interventions for chronic pain.