This study aimed to carry out a systematic review to analyze, describe and discuss the effect of physical fatigue on the performance of soccer players. For this systematic review, searches were performed in Pubmed, Web of Science and SPORTDiscus electronic database until October 3, 2020, following the guidelines of PRISMA. A total of 12 articles met the inclusion criteria: i) healthy soccer players from any age group, competitive level or sex; ii) exposure to physical fatigue; iii) pre and post-physical fatigue conditions; iv) players’ cognitive, technical, physical and tactical performances and v) no restrictions regarding the study design. The results section was organized in four main dimensions: cognitive, technical, physical and tactical. Studies on cognitive performance have shown divergent results, varying according to the cognitive task employed and the physical protocol used. Regarding technical performance, negative effects of physical fatigue were found on the technical fundamentals of the pass, dribble and kick. With regard to physical performance, studies have shown a reduction in sprint capacity and distances covered at high velocity. Finally, the only study that analyzed the tactical performance in the field showed an increase in the team’s collective tactical behavior, but did not include analysis of the players’ individual tactical actions. In summary, the results of the analyzed studies show that the effect of physical fatigue on cognitive performance is inconclusive and that technical and physical performance are negatively affected. Regarding tactical performance, there is a lack of information on the topic in the current literature.