While the benefits of active learning to student experiences are well documented, less is known about active learning in online education, especially regarding the development of 21st century skills (e.g., communication, collaboration, critical thinking, creativity). Specifically, open questions remain concerning the contribution of different active learning pedagogies to different sets of skills in online Science, Technology, Engineering, and Mathematics (STEM) education. The current research addresses this gap. We surveyed 744 undergraduate students to evaluate the relationship between learning design, 21st century skill development, and satisfaction in the context of a course taken remotely during the COVID-19 pandemic (Spring 2020). Using an exploratory and a confirmatory factor analysis as well as several multiple linear regressions, we extracted the relationship between various properties of course design (e.g., frequency of groupwork) and the self-reported development of key 21st century skills. Results show that these skills can be grouped into three sets: communication and collaboration skills, domain-general skills, and STEM-specific skills. We further found that designs for active learning explain variance in students' development of 21st century skills. Specifically, individual work, group work, long-term work, and synchronous work explain variance in students' reports of skill development. Moreover, supporting students in skill development was associated with greater satisfaction with the course. Our findings suggest that activities in the higher levels of the Interactive, Constructive, Active, and Passive framework (ICAP; Chi et al., 2018) are associated with greater learning of key 21st century skills and increase students' satisfaction. We discuss implications for design and institutional support. [Note: The page range (4-31) shown on the PDF is incorrect. The correct page range is 4-29.]