High-quality instructional interaction, in which teachers engage children in conversations that support the development of higher order thinking skills, conceptual understanding, and advanced language skills, is associated with positive outcomes for preschool children. Classrooms serving low-income preschoolers tend to have lower levels of this kind of instruction and yet research suggests that it may be particularly important for these children. The aim of this study was to examine variation in the quality of instructional interactions in Head Start classrooms across different types of teacher-directed activities. Twenty-four Head Start classrooms were observed across four activity types (circle time, math activities, science activities, and storybook reading), and quality of instructional interaction was assessed using the Instructional Support domain of the Classroom Assessment Scoring System. Science activities and storybook reading were associated with higher quality instructional interaction compared with circle time, controlling for teacher characteristics and classroom contextual factors. Math activities were not associated with higher quality instructional interaction compared with circle time. Science and storybook reading may be natural entry points for supporting higher quality instructional interaction in Head Start classrooms.