Background Developing effective, widely useful, weight management programs is a priority in health care because obesity is a major health problem. Objective This study developed and investigated a new, comprehensive, multifactorial, daily, intensive, psychologist coaching program based on cognitive behavioral therapy (CBT) modules. The program was delivered via the digital health care mobile services Noom Coach and InBody. Methods This was an open-label, active-comparator, randomized controlled trial. A total of 70 female participants with BMI scores above 24 kg/m2 and no clinical problems besides obesity were randomized into experimental and control groups. The experimental (ie, digital CBT) group (n=45) was connected with a therapist intervention using a digital health care service that provided daily feedback and assignments for 8 weeks. The control group (n=25) also used the digital health care service, but practiced self-care without therapist intervention. The main outcomes of this study were measured objectively at baseline, 8 weeks, and 24 weeks and included weight (kg) as well as other body compositions. Differences between groups were evaluated using independent t tests and a per-protocol framework. Results Mean weight loss at 8 weeks in the digital CBT group was significantly higher than in the control group (–3.1%, SD 4.5, vs –0.7%, SD 3.4, P=.04). Additionally, the proportion of subjects who attained conventional 5% weight loss from baseline in the digital CBT group was significantly higher than in the control group at 8 weeks (32% [12/38] vs 4% [1/21], P=.02) but not at 24 weeks. Mean fat mass reduction in the digital CBT group at 8 weeks was also significantly greater than in the control group (–6.3%, SD 8.8, vs –0.8%, SD 8.1, P=.02). Mean leptin and insulin resistance in the digital CBT group at 8 weeks was significantly reduced compared to the control group (–15.8%, SD 29.9, vs 7.2%, SD 35.9, P=.01; and –7.1%, SD 35.1, vs 14.4%, SD 41.2, P=.04). Emotional eating behavior (ie, mean score) measured by questionnaire (ie, the Dutch Eating Behavior Questionnaire) at 8 weeks was significantly improved compared to the control group (–2.8%, SD 34.4, vs 21.6%, SD 56.9, P=.048). Mean snack calorie intake in the digital CBT group during the intervention period was significantly lower than in the control group (135.9 kcal, SD 86.4, vs 208.2 kcal, SD 166.3, P=.02). Lastly, baseline depression, anxiety, and self-esteem levels significantly predicted long-term clinical outcomes (24 weeks), while baseline motivation significantly predicted both short-term (8 weeks) and long-term clinical outcomes. Conclusions These findings confirm that technology-based interventions should be multidimensional and are most effective with human feedback and support. This study is innovative in successfully developing and verifying the effects of a new CBT approach with a multidisciplinary team based on digital technologies rather than standalone technology-based interventions. Trial Registration ClinicalTrials.gov NCT03465306; https://clinicaltrials.gov/ct2/show/NCT03465306