An optimal protocol of adding wide-field irradiation to multi-agent chemotherapy for dogs with lymphoma has not been established. The aim of this retrospective case-control study was to evaluate the efficacy of a protocol combining chemotherapy and half-body irradiation (HBI) for dogs with high-grade lymphoma. Dogs in the treatment group received cranial HBI 2 weeks after completing the second cycle of the multi-agent chemotherapy protocol. The radiation therapy protocol consisted of 4 Gy/fraction once per day for 2 consecutive days for the cranial half body, followed by the same protocol for the caudal half 2 weeks later. The control group only received multi-agent chemotherapy. All patients were required to have cytological confirmation of high-grade lymphoma and achieve complete remission after two cycles of multi-agent chemotherapy. Fourteen patients receiving HBI and 11 patients in the control group were included. The median progression-free interval (PFI) in the HBI group (1143 days) was significantly longer than that in the control group (316 days, p = 0.004). In the HBI group, dogs with T cell lymphoma had statistically shorter PFI (292 days) than dogs with B cell lymphoma (2127 days, p = 0.0013). The median survival time in the HBI group (1924 days) was significantly longer than that in the chemotherapy-only group (566 days, p = 0.0077). The predictive factors for longer PFI and ST were found in the patients who received HBI and chemotherapy (p = 0.0062 and 0.0252, respectively). For chemotherapy-responding patients that completed a multi-agent protocol, HBI significantly prolonged the time to tumour relapse compared with the chemotherapy-only group.