Despite the increased mortality due to ST-segment elevation myocardial infarction (STEMI) in South Africa (SA), SA lacks comprehensive data on STEMI clinical outcomes. This study aimed to determine the 30-day and one-year all-cause mortality rates of STEMI patients presenting to our hospital. This was a one-year prospective single-centre study of STEMI patients presenting to the Charlotte Maxeke Johannesburg Hospital in SA between December 2021 and August 2023. We compared the baseline clinical characteristics, reperfusion strategies, and in-hospital, 30-day, and one-year clinical outcomes of survivors and non-survivors. This cohort included 378 STEMI participants. The in-hospital, 30-day, and one-year all-cause mortality rates were 6.6% (n = 25), 10.1% (n = 38), and 17.2% (n = 65), respectively. The pharmacoinvasive strategy was the most used reperfusion therapy (n = 150, 39.7%). On adjusted multivariate Cox regression analysis, a Killip class >2 was the strongest independent predictor of 30-day [HR 5.61, 95% CI 2.83–11.12; p < 0.001] and one-year all-cause mortality [HR 1.72, 95% CI 1.26–2.34; p = 0.001]. Although mortality has increased, our mortality rates were comparable to outcomes from high-income countries but significantly lower than reports from other low- or middle-income countries. Importantly, there were no significant differences in 30-day and one-year survival outcomes between the different reperfusion strategies.