This sequential explanatory mixed methods study with a complementarity rationale examined the differential experiences of MTSS implementation in three Positive Behavior Interventions and Supports (PBIS)-implementing and three non-implementing secondary schools in the Midwestern United States. Using a survey and follow-up interviews with a sample of 25 secondary school leadership team (SLT) members, this study sought to understand (1) their beliefs and attitudes toward MTSS prior to implementation and (2) unique barriers and facilitators to MTSS implementation in secondary education following initial MTSS implementation. Overall, the results of this study indicated that generally, SLT members had positive beliefs and attitudes toward MTSS prior to implementation which were maintained a year later at follow-up. Additionally, several differential barriers and facilitators to implementation emerged between PBIS and non-PBIS schools, though shared barriers and facilitators were also evident. Lastly, experience with PBIS differentially impacted the experiences of SLT members from PBIS and non-PBIS schools. Implications for secondary school practitioners, schools, and local educational agencies are discussed.