The objective of this study was to investigate the effects of the interaction between corn grain processing and protein source on feed intake, growth performance, rumen fermentation, and blood metabolites of dairy calves. Seventy-two 3-day-old Holstein calves with an initial weight of 39.1 ± 3.24 kg were randomly assigned (n = 12 calves (6 male and 6 female) per treatment) to a 2 × 3 factorial arrangement of treatments with the factors of physical form of the corn grain [coarsely ground (CG) and steam-flaked (SF)] and protein type [canola meal (CAN), canola meal + soybean meal (CASY), and soybean meal (SOY)] were assigned. The study showed a significant correlation between corn grain processing method and protein source on calf performance, including starter feed intake, total dry matter intake (DMI), body weight, average daily gain (ADG), and feed efficiency (FE). The CG-CAN and SF-SOY treatments resulted in the highest feed intake and DMI in the post-weaning and total period, respectively. Interestingly, corn processing did not affect feed intake, ADG, and FE, but the highest ADG was observed at SF-SOY and CG-CAN. In addition, the interaction between corn processing method and protein source improved FE in calves fed CG-CAN and SF-SOY during the preweaning period and throughout the period. Although skeletal growth parameters were unchanged, calves fed SOY and CASY had greater body length and withers height than calves fed CAN during the preweaning period. Rumen fermentation parameters were also not affected by the treatments, except that calves fed CAN had a higher molar proportion of acetate than calves fed SOY and CASY. Corn grain processing and protein source did not affect glucose, blood urea nitrogen (BUN), or β-hydroxybutyrate (BHB) concentrations, except for the highest blood glucose level observed in the CAN treatment and the highest BUN level observed in the preweaned calves fed SOY. However, a two-way interaction was observed for BHB concentration, suggesting that ground corn grain resulted in higher BHB concentration during the preweaning and postweaning periods than steam-flaked corn. In summary, it is recommended to incorporate canola meal with ground corn or soybean meal with steam-flaked corn in calf starters to enhance calf growth.