Ecological systems are complex. Representing heterogeneous knowledge about ecological systems is a pervasive challenge because data are generated from many subdisciplines, exist in disparate sources, and only capture a subset of important interactions underpinning system structure, resilience, and dynamics. Knowledge graphs have been successfully applied to organize heterogeneous data systematically and to predict new linkages representing unobserved relationships in complex systems. Though not previously applied broadly in ecology, knowledge graphs have much to offer in an era of global change when system dynamics are responding to rapid changes across multiple scales simultaneously. We developed a knowledge graph to demonstrate the method’s utility for ecological problems focused on highly pathogenic avian influenza (HPAI), a highly transmissible virus with a broad animal host range, wide geographic distribution, and rapid evolution with pandemic potential. We describe the development of a graph to include a wide range of data related to HPAI including pathogen-host associations, animal species distributions, and human population demographics, using a semantic ontology that defines relationships within the data and between datasets. We use the graph to perform a set of proof-of-concept analyses validating the method and identifying new relationships and features of HPAI ecology, underscoring the generalizable value of knowledge graphs to ecology including their utility in revealing previously known relationships between entities and generating testable hypotheses in support of a deeper mechanistic understanding of ecological systems.