This study assessed workers’ exposure to vehicle exhaust emissions and its health effects at the Lebombo Port of Entry. A quantitative cross-sectional design was adopted, and a structured questionnaire was administered on 209 adult workers to measure their knowledge on vehicle exhaust emissions exposures. Air samples were also collected from the participants using air sampling pumps. Data were analyzed using Statistical Package for Social Sciences, version 27. Logistic regression was performed to examine the association between dependent variables and some sociodemographic factors. Vocational certificates and associate degrees were attributed to workers in the South African Police Services and those in Agriculture: (Odds Ratio) = 2.83%, Confidence Interval (1.41–5.65) and (Odds Ratio) = 4.58%, Confidence Interval (2.10–9.99), respectively. Divorced males had a high level of knowledge and awareness of vehicle exhaust emission and their health effects: (Adjusted Odds Ratio) = 5.31%, Confidence Interval (1.08–26.14). Males had better knowledge of vehicle exhaust emission with carcinogenic effects: (Adjusted Odds Ratio) = 3.28%, Confidence Interval (1.11–9.67). Having an associate’s degree as the highest level of education and irritation of nose and eyes were associated with lower awareness of vehicle exhaust emissions: (Adjusted Odds Ratio) = 0.42%, Confidence Interval (0.19–0.97) and (Adjusted Odds Ratio) = 0.31%, Confidence Interval (0.13–0.76), respectively. The diesel particulate matter concentration was higher during day shifts (0.027 mg/m3) compared to night shifts (0.021 mg/m3), p = 0.001. Seventy-one workers (34%) reported experiencing acute headaches often, and fewer workers (n = 31, 14.8%) reported to have never suffered from an acute headache. A majority of workers (71 (34%)) experienced acute irritation of nose and eyes often compared to a few (33 (16%)) workers who experienced the same less often. In addition, a majority of workers (84 (40.2%)) experienced acute fatigue and nausea often, while fewer workers (37 (17.7%)) experienced fatigue and nausea very often. The majority of workers (n = 116, 55.5%) suffered cough and sneezing more often compared to others. There is an urgent need for improved and effective controls to reduce workers’ exposure to vehicle exhaust emissions.