Two-dimensional (2D) materials have a wide platform in research and expanding nano- and atomic-level applications. This study is motivated by the well-established 2D catalysts, which demonstrate high efficiency, selectivity and sustainability exceeding that of classical noble metal catalysts for the oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and/or hydrogen evolution reaction (HER). Nowadays, the hydrogen evolution reaction (HER) in water electrolysis is crucial for the cost-efficient production of a pure hydrogen fuel. We will also discuss another important point related to electrochemical carbon dioxide and nitrogen reduction (ECR and N2RR) in detail. In this review, we mainly focused on the recent progress in the fuel cell technology based on 2D materials, including graphene, transition metal dichalcogenides, black phosphorus, MXenes, metal-organic frameworks, and metal oxide nanosheets. First, the basic attributes of the 2D materials were described, and their fuel cell mechanisms were also summarized. Finally, some effective methods for enhancing the performance of the fuel cells based on 2D materials were also discussed, and the opportunities and challenges of 2D material-based fuel cells at the commercial level were also provided. This review can provide new avenues for 2D materials with properties suitable for fuel cell technology development and related fields.