A 3 yr study evaluated the effects of three preweaning injections of bovine ST, administered 14 d apart, on growth and reproductive performance of Bos indicus-influenced beef heifers. On d 0 of each year, suckling Angus × Brangus heifers (n = 15 heifers/treatment/yr) were stratified by BW (147 ± 20 kg) and age (134 ± 11 d) and randomly assigned to receive an s.c. injection of saline (SAL; 5 mL; 0.9% NaCl) or 250 mg of sometribove zinc (BST; Posilac, Elanco, Greenfield, IN) on d 0, 14, and 28. Heifers and respective dams were managed as a single group on bahiagrass (Paspalum notatum) pastures from d 0 until weaning (d 127). From d 127 to 346, heifers were grouped by treatment, allocated to bahiagrass pastures (1 pasture/treatment/yr) and fed a molasses-based supplement (2.9 kg/heifer daily; DM basis) until d 346. Blood samples were collected on d 0, 14, 28, 42, and then every 9-10 d from d 179 to 346. In yr 3, liver biopsy samples were collected on d 0, 42, and 263. Heifers were exposed to mature Angus bulls from d 263 to 346. Growth performance and physiological parameters were analyzed using the MIXED procedure, whereas reproductive variables were analyzed using the GLIMMIX procedure of SAS. Effects of treatment × year and treatment × year × time were not detected for any variable measured in this study (P ≥ 0.14), except for calving percentage (P = 0.03). Heifers assigned to BST injections had greater overall plasma concentrations of IGF-1 and ADG from d 0 to 42 (P ≤ 0.05), less ADG from d 42 to 127 (P = 0.04), but had similar BW at weaning and postweaning ADG (P ≥ 0.25) compared to SAL heifers. Heifers assigned to BST tended to achieve puberty 26 d earlier (P = 0.10), had greater percentage of pubertal heifers on d 244, 263, 284, and 296 (P ≤ 0.04), tended to have greater overall pregnancy percentage (P = 0.10), and had greater (P ≤ 0.05) calving percentages in yr 1 and 2 (but not yr 3; P = 0.68) compared to SAL heifers. Liver mRNA expression of GHR-1B and IGF-1 on d 0 and 42 did not differ between treatments (P ≥ 0.15), but was greater for BST vs. SAL heifers on d 263 (P ≤ 0.02). Hence, administering three injections containing 250 mg of sometribove zinc at 14 d intervals before weaning (between 135 and 163 d of age) induced long-term impacts on liver gene expression and may be a feasible management practice to enhance puberty and pregnancy attainment in B. indicus-influenced replacement beef heifers.