Background Low-carbohydrate ketogenic diets are a viable method to lose weight that have regained popularity in recent years. Technology in the form of mobile health (mHealth) apps allows for scalable and remote delivery of such dietary interventions and are increasingly being used by the general population without direct medical supervision. However, it is currently unknown which factors related to app use and user behavior are associated with successful weight loss. Objective First, to describe and characterize user behavior, we aim to examine characteristics and user behaviors over time of participants who were enrolled in a remotely delivered clinical weight loss trial that tested an mHealth ketogenic diet app paired with a breath acetone biofeedback device. Second, to identify variables of importance to weight loss at 12 weeks that may offer insight for future development of dietary mHealth interventions, we aim to explore which app- and adherence-related user behaviors characterized successful weight loss. Methods We analyzed app use and self-reported questionnaire data from 75 adults with overweight or obesity who participated in the intervention arm of a previous weight loss study. We examined data patterns over time through linear mixed models and performed correlation, linear regression, and causal mediation analyses to characterize diet-, weight-, and app-related user behavior associated with weight loss. Results In the context of a low-carbohydrate ketogenic diet intervention delivered remotely through an mHealth app paired with a breath acetone biofeedback device, self-reported dietary adherence seemed to be the most important factor to predict weight loss (β=–.31; t54=–2.366; P=.02). Furthermore, self-reported adherence mediated the relationship between greater app engagement (from c=–0.008, 95% CI –0.014 to –0.0019 to c’=–0.0035, 95% CI –0.0094 to 0.0024) or higher breath acetone levels (from c=–1.34, 95% CI –2.28 to –0.40 to c’=–0.40, 95% CI –1.42 to 0.62) and greater weight loss, explaining a total of 27.8% and 28.8% of the variance in weight loss, respectively. User behavior (compliance with weight measurements and app engagement) and adherence-related aspects (breath acetone values and self-reported dietary adherence) over time differed between individuals who achieved a clinically significant weight loss of >5% and those who did not. Conclusions Our in-depth examination of app- and adherence-related user behaviors offers insight into factors associated with successful weight loss in the context of mHealth interventions. In particular, our finding that self-reported dietary adherence was the most important metric predicting weight loss may aid in the development of future mHealth dietary interventions. Trial Registration ClinicalTrials.gov NCT04165707; https://clinicaltrials.gov/ct2/show/NCT04165707 International Registered Report Identifier (IRRID) RR2-10.2196/19053