Objective: To evaluate treatment outcomes and prognostic factors in patients with ultra-high-risk gestational trophoblastic neoplasia (GTN) compared to those with low-risk and high-risk GTN. Methods: A retrospective review of medical records was conducted for GTN patients treated at Chiang Mai University Hospital, Chiang Mai, Thailand, between January 1999 and December 2019. Overall and risk-specific survival rates were estimated using the Kaplan–Meier method, and prognostic factors were analyzed through univariate and multivariate analyses. Results: During the study period, 160 patients with GTN were identified, including 98 (61.2%) classified as low-risk, 31 (19.4%) as high-risk, and 31 (19.4%) as ultra-high-risk. One patient in the low-risk group and one in the high-risk group underwent hysterectomy without adjuvant chemotherapy due to spontaneous regression of serum β-hCG (human chorionic gonadotropin). Additionally, one patient with ultra-high-risk GTN died before receiving chemotherapy. Among the 97 low-risk GTN patients, 80 (82.5%) were treated with either single-agent methotrexate or actinomycin D. Among the 30 high-risk GTN patients, 20 (66.7%) received EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine) as first-line chemotherapy, while 24 (80%) of the 30 ultra-high-risk GTN patients received EMA/CO as first-line treatment. Following first-line chemotherapy and/or salvage treatment, patients with ultra-high-risk GTN had significantly worse outcomes compared with those with low- and high-risk GTN, with remission rates of 63.3%, 96.9%, and 80.0%, respectively (p < 0.01). The five-year overall survival rate for patients with ultra-high-risk GTN was significantly lower than that for patients with low- and high-risk GTN (56% vs. 96% and 80%, respectively; p < 0.001). On multivariable analysis, significant prognostic factors included antecedent term pregnancy (hazard ratio [HR] = 11.50; 95% confidence interval [CI], 3.56–37.22; p < 0.01) and brain metastasis (HR = 4.61; 95% CI, 1.73–12.28; p < 0.01). Conclusions: Ultra-high-risk GTN accounts for only a small proportion of GTN cases but it is associated with poor survival rate and responsible for the majority of GTN-related deaths. Antecedent term pregnancy and brain metastasis were identified as significant prognostic factors.