Due to insufficient dry matter intake and heightened nutrient requirements in early lactation, periparturient dairy cows mobilize adipose and muscle tissues to bridge energy and amino acid gaps, respectively. Our objective was to evaluate the relationship between the relative muscle thickness of late pregnant cows and their early lactation performance. At 35 d before expected calving (BEC), longissimus dorsi muscle thickness (LDT) was measured in forty-one multiparous Holstein cows via ultrasound. Tissue mobilization was evaluated via ultrasound images of LDT and backfat thickness (BFT) at 21 and 7 d BEC as well as at 0, 10, 30, and 60 DIM. Plasma concentrations of 3-methylhistidine (3-MH), creatinine (CRE), non-esterified fatty acids (NEFA), and β-hydroxybutyrate (BHB) were evaluated weekly. Milk yield and milk component data were collected through 60 DIM. Cattle were assigned post hoc to high-muscle (HM; n = 20; LDT > 4.49 cm) or low-muscle (LM; n = 21; ≤4.37 cm) groups, with mean LDT at 35 d BEC greater in HM (5.05 ± 0.49) than in LM (3.52 ± 0.65) animals. Between 35 and 21 d BEC, LM cows gained LDT, whereas HM cows gained BFT. HM cows mobilized more muscle from 21 d BEC to 30 DIM, as reflected by a greater loss of LDT, greater 3-MH concentrations (532 vs. 438 ± 30 ng/mL), and a greater 3-MH:CRE ratio (0.164 vs. 0.131 ± 0.008) in the first three weeks postpartum. The LDT and BFT at 21 d BEC were related to the amount of respective tissue mobilized through 30 DIM (R2 = 0.37 and 0.88, respectively). Although calves born to HM cattle were larger (45.2 vs. 41.8 ± 0.7 kg), HM cows produced less milk (38.8 vs. 41.6 ± 0.8 kg/d) with a tendency towards higher fat content (4.33 vs. 4.05 ± 0.12%), likely related to the mobilization of more backfat from 0 to 60 DIM (1.78 vs. 0.68 ± 0.34 mm), compared to LM cattle. These findings suggest that a cow’s metabolic status, as measured by LDT and BFT prepartum, may influence the metabolic strategy the animal uses to meet energy and amino acid requirements in late gestation and early lactation.