The present study was an attempt to investigate the effect of Problem-Based Learning (PBL), Predict, Observe, Explain (POE), and the combination of both (PBLPOE) on students' critical thinking skills and scientific attitudes in Biology. A pretest-posttest nonequivalent control group design was employed in this study and 132 tenth-grade students from Bengkulu, Indonesia was involved. This study was carried out from February to June 2018. An essay test was administered to assess the participants' critical thinking skills, and a checklist and an interview guideline were used to observe the students' scientific attitudes. The results of the ANCOVA analysis showed that PBL, POE, and PBLPOE had an effect on the students' critical thinking skills and scientific attitudes in Biology with p-value<0.005. The results of the LSD test indicated that PBLPOE was not significantly different from PBL, but differed considerably from POE and conventional in improving students' critical thinking. Also, LSD test on the students' scientific attitudes showed that PBLPOE differed significantly from PBL, POE, and conventional in enhancing students' scientific attitudes. The highest post-test score was observed in the PBLPOE classroom. Therefore, PBLPOE can be used to improve students' performance in Biology.