In this paper, we conduct a comparative analysis to examine the characteristics and evolutionary trends of open access (OA) publications in natural and social sciences. We use data recorded by Science Citation Index Expanded, Social Sciences Citation Index, and Journal Citation Reports during 2001–2015 as the main source. We then comparatively analyse the characteristics of natural and social sciences in terms of historical evolution, main contributors, and distribution of OA journals and publications across different languages, disciplines, and impact factor quartiles. Our results suggest that both natural and social sciences experienced dramatic growth of OA journals since 2009, but the share of social science OA journals within journal impact factor quartile 1 is much lower than that of natural sciences. While natural and social sciences share some similarities in OA publishing activities, such as main countries of contribution, they differ greatly in dimensions such as OA ratio across specific disciplines, countries, and publishing languages. We acknowledge that OA publishing offers a level playing field for traditionally disadvantaged languages, countries, and scientific disciplines, but meanwhile, the advancement of high‐quality OA publishing needs more targeted and sophisticated approaches to tackle differences in natural and social sciences.