The objectives of this study were to investigate the effect of starch and protein interaction on rumen environment, in situ digestion, and total-tract digestibility of nutrients in weaned dairy calves between 8 and 16 wk of age. Sixteen rumen-cannulated calves were randomly divided into 4 dietary treatment groups with 4 calves fed in each treatment. The treatment diets had 2 levels of starch [18%, low starch (LS), or 38%, high starch (HS)] and 2 levels of protein [16%, low protein (LP), or 22%, high protein (HP)] on a dry matter (DM) basis in calf grower: (1) LPLS, (2) LPHS, (3) HPLS, and (4) HPHS. Calves were fed for ad libitum intake (95% assigned grower and 5% grass hay), and refusals were collected weekly. Total-tract digestibility collection and in situ digestibility procedures were performed for each calf at 11 and 15 wk. Samples for in situ digestibility, grass hay (GH), soybean hulls (SBH), wheat middlings (WM), ground corn (GrC), and soybean meal (SBM) were incubated for 9 and 24 h. There was no starch and protein interaction on total-tract digestibility of calves. Total-tract DM, neutral detergent fiber (NDF) and acid detergent fiber (ADF) digestibility, and feed efficiency were affected by both protein and starch inclusion level in calf diet. Total-tract starch digestibility was lower for LS diets. Dry matter digestibility and feed efficiency were greater in calves fed HP and HS diets compared with calves fed LP and LS diets, respectively. Fiber digestibility (NDF and ADF) was less in calves fed HS diets compared with calves fed LS diets but was greater in calves fed HP diets compared with calves fed LP diets. Level of protein did not affect in situ DM and NDF disappearance of GH, but HP increased in situ DM and NDF disappearance of SBH. High-starch diets decreased DM and NDF disappearance of both GH and SBH. At 20 h after feeding, ruminal pH was 0.51 unit higher in calves fed HPHS compared with calves fed LPHS. Total ruminal VFA and proportion of propionate was greater with HS versus LS, whereas proportion of acetate was greater with LS versus HS. The DM disappearance of SBM and WM and NDF disappearance of WM was greater for calves fed HPHS compared with calves fed LPHS at 11 wk of age. In our study, when HP was fed with HS, rumen pH, in situ digestion of WM and SBM, and total-tract digestion of DM, NDF, and ADF increased. This provides evidence for starch-protein interaction in the rumen of recently weaned dairy calves. Improvements in total-tract and in situ digestibility suggest that both protein and starch levels are important for 8- to 16-wk-old calves.