Due to present youth unemployment in Anambra State, Nigeria, the research investigated science process skills acquisition of secondary school students for their entrepreneurship development. Three research questions guided the study and three hypotheses were tested at 0.05 alpha levels. A descriptive survey design was adopted in which a sample of 528 students in the state was used. Data were collected using Science Process Skills Test (SPST) which was validated and reliability index found to be 0.82. Mean, percentage and ANOVA were used for data analysis. The findings revealed that there was a significant difference in the acquisition of five process skills (classification, description, observation, inference and measurement) between male and female students; and a significant interaction between gender and school location in the acquisition of all the skills except observation skill. The study recommended that curriculum planners should identify what skills to be inculcated into the students from specific topics.