BACKGROUND: There is a need to develop interventions to reduce the risk of dementia in the community by addressing lifestyle factors and chronic diseases over the adult life course. OBJECTIVE: This study aims to evaluate a multidomain dementia risk reduction intervention, Body Brain Life in General Practice (BBL-GP), targeting at-risk adults in primary care. METHODS: A pragmatic, parallel, three-arm randomized trial involving 125 adults aged 18 years or older (86/125, 68.8% female) with a BMI of ≥25 kg/m2 or a chronic health condition recruited from general practices was conducted. The arms included (1) BBL-GP, a web-based intervention augmented with an in-person diet and physical activity consultation; (2) a single clinician-led group, Lifestyle Modification Program (LMP); and (3) a web-based control. The primary outcome was the Australian National University Alzheimer Disease Risk Index Short Form (ANU-ADRI-SF). RESULTS: Baseline assessments were conducted on 128 participants. A total of 125 participants were randomized to 3 groups (BBL-GP=42, LMP=41, and control=42). At immediate, week 18, week 36, and week 62 follow-ups, the completion rates were 43% (18/42), 57% (24/42), 48% (20/42), and 48% (20/42), respectively, for the BBL-GP group; 71% (29/41), 68% (28/41), 68% (28/41), and 51% (21/41), respectively, for the LMP group; and 62% (26/42), 69% (29/42), 60% (25/42), and 60% (25/42), respectively, for the control group. The primary outcome of the ANU-ADRI-SF score was lower for the BBL-GP group than the control group at all follow-ups. These comparisons were all significant at the 5% level for estimates adjusted for baseline differences (immediate: difference in means -3.86, 95% CI -6.81 to -0.90, P=.01; week 18: difference in means -4.05, 95% CI -6.81 to -1.28, P<.001; week 36: difference in means -4.99, 95% CI -8.04 to -1.94, P<.001; and week 62: difference in means -4.62, 95% CI -7.62 to -1.62, P<.001). CONCLUSIONS: A web-based multidomain dementia risk reduction program augmented with allied health consultations administered within the general practice context can reduce dementia risk exposure for at least 15 months. This study was limited by a small sample size, and replication on a larger sample with longer follow-up will strengthen the results. TRIAL REGISTRATION: Australian clinical trials registration number (ACTRN): 12616000868482; https://anzctr.org.au/ACTRN12616000868482.aspx.