The ability to think critically is one of the fundamental abilities needed in the workplace. The development of critical thinking skills (CTS) among Nigerian secondary school students is having little effect as current practice of teaching is ‘conventional’ that do not promote the development of skills. In order to replace rote learning, a new approach to teaching and learning is needed that places more emphasis on learning, comprehending and measuring skills. It was believed by many educators that 6E Inquiry-Based Learning (6EIBL) is capable of promoting critical thinking skills among learners. Numerous studies have documented the benefits of critical thinking in raising student achievement, in addition to the urgent need to address poor critical thinking among Nigerian secondary school students. Educators in Nigeria are required to use instructional strategies that motivate and help students build a strong sense of critical thinking to appreciate and value the sciences. Contrary to expectations in earlier researches, the effect of 6EIBL on increasing students' levels of critical thinking in science subjects especially biology at the secondary school level in Nigeria has not been demonstrated. This study compares the effect of 6EIBL with conventional teaching methods on students' critical thinking in learning biology among 80 fourth-grade students A non-equivalent control group design was adopted. Purposive sampling was used in two schools to compose experimental and control groups. Each intact class contains 40 participants. The data was obtained using the Photosynthesis Critical Thinking Questionnaire PCTQ). Descriptive statistics and the sample t-test were used to examine the variables. The findings showed that 6EIBL increases students' critical thinking abilities to solve photosynthesis problems. Additionally, students in the experimental group performed better in conducting experiments and other activities and retained the skills more than students in the control group.