Background The advent of tirzepatide has transformed obesity care; yet, real-world weight loss outcomes necessarily depend on patient engagement with behavioral support. Digital platforms offering coaching, self-monitoring, and automated feedback have the potential to further augment pharmacological efficacy. Objective The aim of the study is to examine associations between digital engagement and weight loss outcomes among adults prescribed tirzepatide in routine care over 12 months and to identify baseline correlates of engagement. Methods In this retrospective cohort study, we included adults (18-75 years; BMI ≥30 or ≥27.5 kg/m2 with comorbidities) who initiated tirzepatide between February 2024 and August 2025 via a UK digital weight loss service. Engagement was defined by all 3: attendance at ≥1 coaching session AND ≥1 weekly weight log AND ≥1 app login over 12 months. Percent weight loss was analyzed at months 2, 4, 6, 8, 10, and 12 using a mixed model repeated measures adjusted for age, sex, baseline BMI, and comorbidities. Time-to-event analyses (Kaplan-Meier) assessed attainment of ≥5%, ≥10%, ≥15%, and ≥20% weight loss thresholds. Multivariable logistic regression identified correlates of engagement, reporting odds ratios (ORs) per decade of age and per 5 kg/m2 BMI. Results Among 126,553 participants, 6746 (5.3%) were maximally engaged. Cohort demographics were a mean age of 42.3 (SD 12.4) years, 78.9% (99,905/126,553) female, and a mean BMI of 35.3 (SD 6.2) kg/m2. Engaged users achieved greater adjusted weight loss at month 12 (–22.9%, 95% CI –23.2 to –22.6) versus nonengaged users (–17.5%, 95% CI –17.7 to –17.4), an absolute difference of 5.3 percentage points (P<.001; Cohen d=0.54). Differences emerged by month 2 (–7.4% vs –6.4%; P<.001) and widened steadily. Engaged participants reached all clinically significant weight loss thresholds faster (5%-20%; log-rank P<.001), and engaged participants were nearly 3 times more likely to achieve ≥20% weight loss compared to nonengaged participants (1079/6746, 16% vs 6710/119,807, 5.6%; risk ratio 2.88; P<.001). Older age (OR 1.18 per decade, 95% CI 1.15-1.20; P<.001), higher BMI (OR 1.14 per 5 kg/m2, 95% CI 1.12-1.16; P<.001), and the presence of polycystic ovary syndrome (OR 1.59, 95% CI 1.45-1.74; P<.001) or fatty liver disease (OR 1.52, 95% CI 1.32-1.76; P<.001) correlated with engagement. Male sex (OR 0.86, 95% CI 0.81-0.92; P<.001) and diabetes (OR 0.83, 95% CI 0.73-0.95; P=.009) were associated with lower engagement. Conclusions Digital engagement was associated with substantially greater tirzepatide-associated weight loss in real-world practice. Integrating structured digital support with pharmacotherapy represents a promising strategy for optimizing obesity management.