Chemistry is a scientific discipline that is often considered difficult because students struggle to solve contextual and open-ended problems, mainly due to a poor understanding of scientific concepts related to the problem. To fully grasp the concepts in chemistry, students must develop the ability to solve real-life problems. Problem-solving skills are applied in many aspects of life, making them crucial for the 21st century. Problem-based learning (PBL) is an effective method for improving students’ problem-solving skills. This study aims to outline how the PBL approach enhances students’ problem-solving skills, specifically in the context of chemistry education. The sixteen research articles reviewed in this paper were collected from well-known databases such as ERIC, SCOPUS, and Google Scholar. Systematic literature review (SLR) is the method used in this review. This review provides evidence that PBL can enhance problem-solving skills in chemistry education. All research articles have shown that PBL has a significantly positive effect on the problem-solving skills of students. Seven out of sixteen articles have provided insights into the design and framework of PBL implementation. The researcher recommends conducting more studies in all areas of chemistry to provide clear guidance on incorporating PBL. The researcher also recommends using mobile technologies to integrate PBL in a stimulating manner, such as by developing a mobile application to aid in the instructional process. Proper insights into the effectiveness of implementing PBL to enhance problem-solving skills in chemistry, as well as the integration of PBL into the instructional process, are necessary. This will aid teachers and lecturers in planning their lessons, which is why this systematic review is needed.