Aims/hypothesis The aim of this work was to examine the associations of average weight and weight velocity in three growth periods from birth through adolescence with type 2 diabetes incidence. Methods Child participants were selected from a 43 year longitudinal study of American Indians to represent three growth periods: pre-adolescence (birth to similar to 8 years); early adolescence (similar to 8 to similar to 13 years); and late adolescence (similar to 13 to similar to 18 years). Age-, sex- and height-standardised weight z score mean and weight z score velocity (change/year) were computed for each period. Participants were followed for up to 25 years from the end of each growth period until they developed diabetes. Associations of weight z score mean or weight z score velocity with diabetes incidence were determined with sex-, birth date- and maternal diabetes-adjusted Poisson regression models. Results Among 2100 participants representing the pre-adolescence growth period, 1558 representing the early adolescence period and 1418 representing the late adolescence period, there were 290, 315 and 380 incident diabetes cases, respectively. During the first 10 years of follow-up, the diabetes incidence rate ratio (95% CI) was 1.72 (1.40, 2.11)/SD of log(10) weight z score mean in pre-adolescence, 2.09 (1.68, 2.60)/SD of log(10) weight z score mean in early adolescence and 1.85 (1.58, 2.17)/SD of log(10) weight z score mean in late adolescence. The diabetes incidence rate ratio (95% CI) was 1.79 (1.49, 2.17)/SD of log(10) weight z score velocity in pre-adolescence, 1.13 (0.91, 1.41)/SD of log(10) weight z score velocity in early adolescence and 1.29 (1.09, 1.51)/SD of log(10) weight z score velocity in late adolescence. There were strong correlations in the weight z score means and weak correlations in the weight z score velocities between successive periods. Conclusions/interpretation Higher weight and accelerated weight gain in all growth periods associate with increased type 2 diabetes risk. Importantly, higher weight and greater weight velocity during pre-adolescence jointly associate with the highest type 2 diabetes risk.