The conceptualization of pre-service teachers' knowledge integration typically involves the distinction of two types: first-order knowledge integration, which includes merging domain-specific knowledge entities into a common knowledge base, and second-order knowledge integration, which refers to the integrated (simultaneous) application of knowledge from diverse domains. This study investigates the effect of instructional prompts in the form of (a) relevance instructions and (b) guiding questions on promoting pre-service teachers' first-order knowledge integration in a reading- and writing-based learning setting with three domain-specific study texts: one text each referring to content knowledge (CK), general pedagogical knowledge (PK), or pedagogical-content knowledge (PCK). Furthermore, the study explores whether pre-service teachers' second-order knowledge integration depends on the degree to which they engaged in first-order knowledge integration when reading and writing about different domain-specific learning contents. The study applied a three parallel group experimental design. An analysis of essays written by N = 83 German language pre-service teachers indicated positive effects of both prompts on first-order knowledge integration. Moreover, a mediation analysis showed that pre-service teachers' second-order knowledge integration is mediated by their first-order knowledge integration. The results are discussed and integrated into the existing body of research, practical implications are presented, and limitations of the study are explained.