Background: Over the long term, unhealthy lifestyles can lead to many health problems, especially type 2 diabetes (T2D). The aim of the present study was to determine associations between lifestyle factors (smoking, alcohol consumption, physical activity, and diet) and T2D in American adults (aged ≥20 years) in a nationally representative sample. Methods: Data for 12 987 American adults participating in the National Health and Nutrition Examination Survey 2005–2014 were evaluated. Weighted multiple logistic regression models were used to examine associations between the four lifestyle factors and T2D after adjusting for demographics and socioeconomic status (SES). Prevalence trends for T2D were examined using Cochran–Armitage tests. Results: There was a significant increasing prevalence trend for T2D among American adults. Smokers and individuals consuming >12 alcoholic drinks in the past year were less likely to report having T2D than non‐smokers (odds ratio [OR] 0.41; 95% confidence interval [CI] 0.35–0.48) and those consuming(OR 0.46; 95% CI 0.39–0.55). Participants with light physical activity have a greater likelihood of having T2D than those engaging in vigorous physical activity (OR 5.72; 95% CI 4.30–7.60). Individuals consuming a poor diet were more likely to report having T2D than those eating an excellent diet (OR 1.18; 95% CI 1.02–1.41). All these relationships remained significant after adjustment for demographics and SES. Conclusion: All four lifestyle factors were significantly associated with T2D among American adults. The findings of the present study provide useful information for healthcare providers that may help them promote specific lifestyle modifications.