Background: We aimed to investigate the efficacy and safety of home-based oral immunotherapy (OIT) in children with cow’s milk (CM) allergy (CMA) and to examine whether sustained unresponsiveness (SU) could be achieved after cessation of OIT. Methods: Children with CMA, aged 3–10 years, were enrolled in the OIT (n = 8) and the control (n = 8) groups. Patients increased the dose of heated milk daily at home during the build-up phase. During the maintenance phase, 100 mL of unheated milk (UM) (3.0 g of CM proteins) was administered daily to the patients for 12 months. Oral food challenge (OFC) tests were performed with a total dose of 200 mL of UM after the build-up phase and four weeks after cessation of CM following the maintenance phase. Results: All patients in the OIT group achieved desensitization after completion of the build-up phase. After 12 months of the maintenance phase and four weeks of the CM restriction period, OFC was performed in six patients in the OIT group. Among them, five (83.3%) patients obtained SU, while none of the patients in the control group achieved tolerance (p = 0.003). During OIT, adverse reactions were reported in seven (87.5%) patients. Anaphylaxis occurred in three (37.5%) patients in the OIT group and in four (50.0%) patients in the control group (p = 1.000). There were no serious adverse or life-threatening events during OIT. Conclusions: Home-based milk OIT is an effective and safe treatment method for SU and desensitization to CMA.