Background The prevalence of obesity is rising. Most previous studies that examined the relations between BMI and physical activity (PA) measured BMI at a single timepoint. The association between BMI trajectories and habitual PA remains unclear. Objective This study assesses the relations between BMI trajectories and habitual step-based PA among participants enrolled in the electronic cohort of the Framingham Heart Study (eFHS). Methods We used a semiparametric group-based modeling to identify BMI trajectories from eFHS participants who attended research examinations at the Framingham Research Center over 14 years. Daily steps were recorded from the smartwatch provided at examination 3. We excluded participants with <30 days or <5 hours of smartwatch wear data. We used generalized linear models to examine the association between BMI trajectories and daily step counts. Results We identified 3 trajectory groups for the 837 eFHS participants (mean age 53 years; 57.8% [484/837] female). Group 1 included 292 participants whose BMI was stable (slope 0.005; P=.75), group 2 included 468 participants whose BMI increased slightly (slope 0.123; P<.001), and group 3 included 77 participants whose BMI increased greatly (slope 0.318; P<.001). The median follow-up period for step count was 516 days. Adjusting for age, sex, wear time, and cohort, participants in groups 2 and 3 took 422 (95% CI –823 to –21) and 1437 (95% CI –2084 to –790) fewer average daily steps, compared with participants in group 1. After adjusting for metabolic and social risk factors, group 2 took 382 (95% CI –773 to 10) and group 3 took 1120 (95% CI –1766 to –475) fewer steps, compared with group 1. Conclusions In this community-based eFHS, participants whose BMI trajectory increased greatly over time took significantly fewer steps, compared with participants with stable BMI trajectories. Our findings suggest that greater weight gain may correlate with lower levels of step-based physical activity.