This study determined the Influence of students’ self-esteem and students’ locus of control and acquisition of employability skills among business education students in Federal Universities South-South Geopolitical Zone of Nigeria. To achieve the purpose of the study, two research questions were raised and two hypotheses were formulated to guide the study. The study adopted a survey research design. The population consisted of four hundred and forty (440) final year business education students in the study area, who were all involved in the study due to the manageable size of the population. A 20-item questionnaire titled “Students’ Self-esteem and Students’ Locus of Control on the Acquisition of Employability Skills’ Scale” (ISSSLCAES) was used for data collection. The internal consistency of the instrument was determined using the Cronbach Alpha statistical technique which yielded an overall reliability coefficient of 0.92 The data collected were analysed using mean (X) and standard deviation (SD) to answer the research questions. Similarly, the null hypotheses were tested at 0.05 level of significance using an independent t-test. The findings from data analysis showed that students’ self-esteem and students’ locus of control significantly influenced the acquisition of employability skills among Business Education students in Federal Universities, South-South Geopolitical Zone of Nigeria with High Influence (HI). While the test of hypotheses revealed that, there is no significant difference in the mean rating of the male and female respondents on the students influence of gender on the acquisition of employability skills. Based on the findings of the study, it was concluded that, the acquisitions of employability skills will help the students of the universities to be self-reliance or to be gainfully employed. It was equally recommended among others that Business Education students should be responsible for enhancing their employability skills so that their employability rate could be enhanced to grab the working opportunity upon graduation.