The goal of the study is to explore the opportunities and challenges associated with Project-Based Learning strategy in a global context on the aspects of both fostering learning community of practices and nurturing the 21st century skills. For collecting empirical data, the study implements and administers an online international project-based learning program for high school students. Since it is claimed that interpersonal interaction is key to the success of online project-based learning programs, the study first focuses on investigating patterns of community of practice, which is a combination of online learning behaviors and interpersonal interaction, among students against a claimed theoretical framework. For unveiling the impacts on fertilizing the 21st century skills, the study examines the perceptions of students and teachers participating in the online international project-based learning program. Results of the study confirm the asserted theoretical framework regarding the community of practices and reveal that students of various countries perform differently in terms of community of practices in virtual learning space. As to building the 21st century skills on students, the study credits the project-based learning strategy deploying in a global context for providing intuitive and essential aspects of learning ingredients to students for pursuing skills related to Communication, Collaboration, Complex Problem-solving, Critical Thinking, and Creativity.