This study aimed to investigate the influence of Project-Based Learning STEM (PjbLSTEM) Applications involving the use of waste materials on the 21st-century skills of 10th-grade students. In line with the purpose of the study, the pre-experimental design was used. The sample consisted of 24 students in total. The 21st-Century Skills Usage Scale, structured and semi-structured interview forms, were used as the data collection tools. During the applications, PjbL-STEM activities were carried out. The data collected were analyzed using the Wilcoxon Signed Ranks Test and the thematic analysis technique. The data analysis revealed a significant increase in the students' 21st-century skills, such as their levels of use of autonomy and cooperation skills and their levels of environmental sensitiveness. The students also reported that the activities had positive effects on many of their 21st-century skills such as communication, and collaboration, problem-solving, creativity, critical thinking, responsibility, environmental awareness, and information-technology literacy. Based on the findings, the following suggestions were put forward: PjbL-STEM activities could be carried out more in educational institutions belonging to the Ministry of National Education. Teacher-training activities could be carried out, and in-service training could be organized to support the application of innovative methods.