Introduction: Sedentary time and time spent in various intensity-specific physical activity are co-dependent, and increasing time spent in one behaviour requires decreased time in another. Objective: The aim of the present study was to examine the theoretical associations with reallocating time between categories of intensities and cardiometabolic risk factors in a large and heterogeneous sample of children and adolescents. Methods: We analysed pooled data from 13 studies comprising 18,200 children and adolescents aged 4–18 years from the International Children’s Accelerometry Database (ICAD). Waist-mounted accelerometers measured sedentary time, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA). Cardiometabolic risk factors included waist circumference (WC), systolic blood pressure (SBP), fasting high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), triglycerides, insulin, and glucose. Associations of reallocating time between the various intensity categories with cardiometabolic risk factors were explored using isotemporal substitution modelling. Results: Replacing 10 min of sedentary time with 10 min of MVPA showed favourable associations with WC, SBP, LDL-C, insulin, triglycerides, and glucose; the greatest magnitude was observed for insulin (reduction of 2–4%), WC (reduction of 0.5–1%), and triglycerides (1–2%). In addition, replacing 10 min of sedentary time with an equal amount of LPA showed beneficial associations with WC, although only in adolescents. Conclusions: Replacing sedentary time and/or LPA with MVPA in children and adolescents is favourably associated with most markers of cardiometabolic risk. Efforts aimed at replacing sedentary time with active behaviours, particularly those of at least moderate intensity, appear to be an effective strategy to reduce cardiometabolic risk in young people.