Key word signing, an unaided augmentative, and alternative communication (AAC) system is commonly used by children with Down syndrome who attend mainstream primary schools. To ensure the successful use of key word signing within a mainstream environment, a meaningful, contextually appropriate sign vocabulary must be available to all communication partners. The aim of this study was to develop a core school-based key word signing vocabulary to facilitate effective communication between children with Down syndrome and their communication partners in the first year of mainstream primary school. Four key groups-participants with Down syndrome, their peers, teachers, and special needs assistants-and a speech-language pathologist contributed to the vocabulary over the course of an academic year, through observations, semi-structured interviews, and guided tours of the school environment. Based on criteria of frequency and commonality, 140 words were considered to be core vocabulary. The current study provides new insights into the complex process of vocabulary selection for children who use key word signing at school and highlights the importance of access to a functional sign vocabulary in facilitating inclusive education practices.