Objectives With the ageing of our population, it seems plausible that the prevalence of both dementia and multimorbidity will increase in the following decades. The aim of this study is to examine the trends in prevalence and incidence of registered dementia and trends in multimorbidity in patients with dementia in general practice in Flanders. Design Retrospective, longitudinal cohort study. Setting Primary care practices across Flanders, Belgium. Participants Patients included in the Intego database. Methods Data were collected from the Intego database, a Belgian general practice registration network, from 1 January 2000 to 31 December 2021. Joinpoint regression, the Cochran-Armitage test and Jonckheere-Terpstra test were used for the trend analysis. Results Data from 149 492 unique patients aged 65 years and older were available. From 2000 to 2021, 3835 incident cases of dementia were found. The age-adjusted prevalence of registered dementia significantly increased during this study period, from 1.19% to 2.43% (average annual percentage change (AAPC) 3.3; 95% CI 2.7 to 4.0). Incidence increased from 3.68 to 5.86 per 1000 patient years overall (AAPC 1.8, 95% CI −2.0 to 5.7), but declined in recent years (annual percentage change −8.1, 95% CI −14.8 to −0.8). Almost three-quarters of the patients with dementia (74.8%) suffered from multimorbidity (three or more comorbidities) and this increased significantly during the study period (p=0.0031). By 2021, 86.7% and 74.8% of the patients with dementia suffered from two or more or three or more chronic conditions, respectively. Hypertension (47.9%), osteoarthritis (29.7%) and lipid metabolism disorders (25.7%) were the most prevalent conditions. Conclusions The prevalence of registered dementia doubled over a 22-year time period, mirroring the increasing health burden by this disease globally. Furthermore, three-quarters of the patients with dementia suffered from multimorbidity, underlining the urgent need to implement comorbidity management and patient-centred care ...