ST-segment depression (ST-D) on the admission electrocardiogram of patients with non-ST-elevation acute coronary syndromes (NSTEACSs) is associated with higher mortality. However, few studies have evaluated the effect of location of ST-D and T-wave polarity on long-term prognosis of patients with NSTEACS. Electrocardiographic (ECG) and clinical data from 6,770 patients with NSTEACS randomly assigned in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIB trial were analyzed retrospectively. One-year mortality was correlated with location of ST-D (leads I and aVL; II, III, and aVF; V1 to V3; or V4 to V6) and T-wave polarity. ST-D in any of the ECG locations was associated with higher mortality compared with patients without ST-D. Patients with ST-D and T-wave inversion in leads V4 to V6 had the highest 1-year mortality rate of all groups (16.2%), significantly higher compared with patients with ST-D without T-wave inversion in those leads (9.0%, p = 0.001). Logistic regression analysis showed that age, hyperlipidemia, Killip class >I, history of myocardial infarction, history of heart failure, history of angina pectoris, systolic blood pressure, heart rate, sum of ST-D (odds ratio 1.061, 95% confidence interval 1.035 to 1.087, p <0.001), and ST-D with T-wave inversion in leads V4 to V6 (odds ratio 1.374, 95% CI 1.023 to 1.844, p = 0.035) were independent predictors of 1-year mortality. Conversely, ST-D without T-wave inversion in leads V4 to V6 or other ECG presentations were not independent predictors of high 1-year mortality. In conclusion, ST-D with T-wave inversion in leads V4 to V6 on the admission electrocardiogram in patients with NSTEACS identifies those with higher 1-year mortality than for patients with any other ECG presentation.