Sweet potato (Ipomoea batatas L.) is a key food security crop in the developing world. Its production is, however, constrained by low-quality, virus-infected planting material derived from conventional vegetative propagation. In this study, we developed an efficient and reproducible in vitro micropropagation protocol for the orange-fleshed sweet potato cv. ‘Kulfo’. Nodal and apical shoot explants were cultured on Murashige and Skoog (MS) medium containing different combinations of 6-benzylaminopurine (BAP), naphthalene acetic acid (NAA), and gibberellic acid (GA₃) for shoot initiation and multiplication, and indole-3-butyric acid (IBA) and NAA for rooting. The maximum shoot regeneration was achieved (62% from nodal and 59% from apical explants) on MS medium supplemented with 0.5 mg L⁻¹ BAP and 0.1 mg L⁻¹ GA₃. MS medium supplemented with 1.0 mg L⁻¹ BAP and 0.1 mg L⁻¹ NAA produced a mean of 7.2 shoots per explant per subculture with vigorous growth during the shoot multiplication stage. Half-strength MS medium supplemented with 0.1 mg L⁻¹ IBA and 0.1 mg L⁻¹ NAA was the best rooting medium. The acclimatized plantlets from the optimal treatment showed a 98.2% survival rate in the greenhouse. The optimized cultivar-specific protocol provides a reliable system for the mass production of high-quality, orange-fleshed sweet potato planting material to support food security, genetic improvement, and germplasm conservation.