The study investigated enhancing entrepreneurship opportunities through chemistry education: Implication for Nigeria youth empowerment in 21st century. Three research questions with their corresponding null hypotheses guided the study. A quasi-experimental, non-randomized control group design was adopted in three intact groups. population of this study was 954 SS 3 chemistry students in Odeda Local Government Area. A sample of 142 chemistry students was drawn using a purposive and simple random sampling techniques from three (3) out of 18 public schools in the LGA. Three intact classes were randomly assigned experimental groups (two classes) and control group (one class). Both experimental and control groups were subjected to pre-and post-testing. A 20-item tagged “Chemistry Practical Skills Acquisition on Soap and Detergent Production” (CPSASDP) structured on a 4-point rating scale developed by the researchers was the instrument used for data collection. It was validated by three experts in chemistry education and measurement and evaluation. The reliability estimate was computed using Cronbach’s Alpha with coefficient index of 0.75. The three groups were taught the same concepts, but with different instructional arrangement. Data collected were analyzed using mean and standard deviation to for answering research questions and Z-test for answering the null hypotheses at 0.05 level of significance. The results revealed that both entrepreneurial skills engagements enhance skills acquisition if appropriately handled. In addition, the hypotheses were accepted because they only differed in their mean score differences. Based on the results, it was recommended among others that students should apply the skills acquired in Chemistry practical to enhance their entrepreneurship development.