Background StudyAs interest in programming education continues to grow, more educators are incorporating programming into K‐12 classrooms. There is evidence that programming can help develop essential skills for future societal advancement, known as 21st century skills. However, there has been limited research into which sub‐skills of 21st century skills are fostered through programming and the effect sizes thereof.ObjectiveThis study presented a meta‐analysis to comprehensively understand the influence of programming instruction in K‐12 classrooms on the development of students' 21st century skills in different dimensions of sub‐skills. And further analysed the impact of key elements of programming instruction design on its effectiveness.MethodsA comprehensive meta‐analysis was conducted, covering 74 empirical studies published between 2000 and 2023, involving 136 effect sizes, and moderation analyzes on variables of instructional design.ResultsThis study indicated that implementing programming instruction in K‐12 schools can help develop students' multiple dimensions of 21st century skills, such as critical thinking, creativity, communication, collaboration, problem‐solving and decision, learning to learn, ICT literacy, and personal and social responsibility. Overall, programming demonstrates a moderate but significant effect on improving 21st century skills (Hedges's g = 0.621, p = 0.000 < 0.01). Furthermore, several best practices were identified to enhance students' 21st century skills, including initiating programming education from kindergarten, limiting the duration of programming interventions to 6 months, adopting interdisciplinary approaches to programming education, utilizing visual programming tools, and selecting appropriate assessment methods.ConclusionBased on these findings, this study recommended the thoughtful design of programming education to maximize its advantages in various dimensions of 21st century skills.