The evolution of multi-tier systems of support (MTSS) for both academics and behavior has reflected the diverse interests of those leading implementation efforts, the influence of various state and local regulatory requirements, and differing funding methods and priorities. These variations have naturally led to many different pathways for implementing MTSS. Although the role of the district in MTSS has varied, many leaders in the field of education consider district leadership and involvement an essential component for successful MTSS implementation. District leadership in MTSS is used to provide schools with political and administrative support, training and technical assistance, layered in-service curricula, data-based decision making systems for ongoing evaluation, and access to interagency relationships for supporting student health and wellbeing. This article addresses the key district mechanisms that are used to integrate academic and behavioral interventions as school personnel learn new strategies for improving outcomes for students.