High prevalence of diabetes mellitus is caused by various factors such as lifestyle changes and obesity, and tends to be higher in urban than in rural areas. The aim of this study was to analyse obesity, physical activity, smoking, and family history as determinants of type 2 diabetes mellitus in Manado City, Indonesia. A matched case-control study of outpatients at five public health centres in Manado City from February to November 2018 was conducted; cases were patients who had been clinically diagnosed with type 2 diabetes mellitus and controls were those without a diagnosis, and these were matched in a 1:1 ratio based on age and sex. Simple random sampling was used with a total of 128 participants, and data were analysed by McNemar’s test and conditional logistic regression. The results showed p-values for obesity of <0.05 (OR=7.75, 95% CI=2.73-21.95), for physical activity of <0.05 (OR=11.00, 95% CI=3.37-35.86), for smoking of 0.208 (OR=1.58, 95% CI=0.76-3.26), and for family history of diabetes mellitus of <0.05 (OR=7.00, 95% CI=2.45-19.95). Multivariate modelling showed physical activity had the highest odds of causing to type 2 diabetes mellitus with OR equals to 7.89. Significant associations were found between obesity, physical activity, and family history with physical activity returning the highest odds. Changes in lifestyle are highly recommended to prevent increased risk of type 2 diabetes mellitus, particularly to include frequent physical activity such as jogging, running, walking, or other aerobic exercise to increase insulin sensitivity.