Secondary school administrators play a vital role as instructional leaders, but little is known about their knowledge of science practices and perceptions of strategies for supporting reform-oriented science instruction. This multiphase, mixed-methods Q-Methodology study explored administrators' perceptions of instructional leadership and, in particular, high-quality science instruction. After a concourse of 40 items was developed through a review of literature and an expert panel, n = 22 administrators from one urban school district completed a Q-sort and a post-sort questionnaire in which they commented on a lesson excerpt. Principal components analysis with varimax rotation was used to assimilate the participants into three factors or groups explaining 40% of the variance. A subsample (n = 14) of administrators then participated in focus groups to engage in collective sensemaking. Although administrators consistently valued positive teacher-student relationships and had high expectations for all students over other managerial duties, perceptions of how to support teachers and their ability to detect evidence-based science pedagogy (NGSS), differed. Administrators with a science background or more experience as an administrator were more familiar with some of the evidence-based instructional strategies for science included in the sample lesson. Administrators without such a background tended to emphasize general pedagogical techniques. We discuss implications for the development of school leaders with varying disciplinary backgrounds as one component of building districts' capacity for high-quality science instruction.