We investigated how differently structured external scripts interact with learners’ internal scripts concerning individual knowledge acquisition in a Web-based collaborative inquiry learning environment. 90 students from two secondary schools participated. Two versions of an external collaboration script (high vs. low structured) supporting collaborative argumentation were embedded within a Web-based collaborative inquiry learning environment. Students’ internal scripts were classified as either high or low structured, establishing a 2x2-factorial design. Results suggest that the high structured external collaboration script supported the acquisition of domain-general knowledge of all learners regardless of their internal scripts. Learners’ internal scripts influenced the acquisition of domain-specific knowledge. Results are discussed concerning their theoretical relevance and practical implications for Web-based inquiry learning with collaboration scripts.