Studies examining the joint associations of lifestyle exposures can reveal novel synergistic and joint effects, but no study has examined the joint association of diet and physical activity (PA) with type 2 diabetes (T2D) and hypertension. The aim of this study is to examine the joint associations of PA and diet with incidence of type T2D and hypertension, as a combined outcome and separately in a large sample of adults in the United Kingdom. This prospective cohort study included 144 288 UK Biobank participants aged 40-69. Moderate to vigorous PA (MVPA) was measured using the International Physical Activity Questionnaire and a wrist accelerometer. We categorized PA and diet indicators (diet quality score [DQS] and energy intake [EI]) based on tertiles and derived joint PA and diet variables. Outcome was major cardiometabolic disease incidence (combination of T2D and hypertension). A total of 14 003 (7.1%) participants developed T2D, 28 075 (19.2%) developed hypertension, and 30 529 (21.2%) developed T2D or hypertension over a mean follow-up of 10.9 (3.7) years. Participants with middle and high self-reported MVPA levels had lower risk of major cardiometabolic disease regardless of diet (eg, among high DQS group, hazard ratios [HRs] in middle and high MVPA group were 0.90; 95% CI, 0.86-0.94), and 0.88 (95% CI, 0.84-0.92), respectively. Participants with jointly high device-measured MVPA and high DQS levels had lower major cardiometabolic disease risk (HR, 0.84; 95% CI, 0.71-0.99). The equivalent joint device-measured MVPA and EI exposure analyses showed no clear pattern of associations with the outcomes. Higher PA is an important component in cardiometabolic disease prevention across all diet quality and total EI groups. The observed lack of association between diet health outcomes may stem from a lower DQS.