The study examines the causes and effects of driver's fatigue on road crashes in south-western Nigeria. The study was carried out in the administrative seats of Oyo and Ogun states of Nigeria with the aid of structured questionnaires which were administered on 325 respondents in the study area using simple random sampling approach. The collected data were analysed using multiple regression model.The study revealed that, duration of driving, stress, sleep deficit, alcohol contributed significantly to the causes of driver's fatigue both at 5% and 10% significant levels.It was concluded that, the safest option is for driver to avoid driving when sleepy on when they are ill or taking medication. And that it is pertinent on them to plan their journeys in such a way that it will include regular rest, break of at least 15 minutes at every two hours.