International research collaboration (IRC) is crucial to improving science and technology (S&T) research capabilities. Existing literature has revealed that several factors influence IRC, but a complete analytical framework has yet to be developed. This study attempts to fill this gap by building a framework to analyze the IRC of China’s State Key Laboratories (SKLs). Based on the external environment oriented toward resource dependence theory and social exchange theory, a questionnaire was designed and deployed within SKLs. Ten hypotheses were established and tested using the structural equation model (SEM) in Amos 23 software. The results showed that, among external environmental factors, China’s S&T policy has facilitated the IRC of SKLs. In addition, international S&T decoupling with China inhibited the IRC of SKLs. Finally, the results showed that COVID-19 did not exert a significant negative influence. Among the social exchange factors, collaboration effects, collaboration reciprocity, and collaboration ties exerted a positive influence on the IRC of SKLs. External environmental factors also worked in tandem with social exchange factors.