Statistics is an essential subject in the educational landscape of Nigeria and a critical topic in the development of scientific reasoning. Perhaps, the students confront statistics with varying attitudes. The purpose of the current study was to investigate the variations in attitude towards statistics based on gender and academic self-efficacy. One hundred and twenty-eight undergraduates pooled from different public universities in the Anambra State of Nigeria participated in the study. A cross-sectional survey design was adopted. The participants completed a self-report measure of Survey of Attitude toward Statistics (SATS-36), initially developed by Schau (2003), and the College Academic Self-Efficacy Scale (CASES) created by (Owen & Froman, 1988). A multiple regression analysis was performed on the data, and the result established a statistically significant interaction between the independent and dependent variables. It was concluded that gender and academic self-efficacy are essential determinants of the variation in attitude towards statistics. The study recommends that relevant persons consider this interactional effect of the variables.