Teaching is a complex activity that demands paying attention to diverse components and relationships that affect the learning process, and acting with intentionality to build and nurture those connections. In this qualitative research study, we proposed and used an intentional–relational framework to explore differences in the relationships that four general chemistry instructors sought and acted to build with intention in their classes. Our goal was not to evaluate the quality of instruction but rather to characterize instructors’ practices to gain insight into educational relationships that may affect student performance. All instructors in our sample manifested a strong interest in helping students succeed in their studies and relied on a variety of resources designed and integrated into their courses to support student learning. They mostly differed in the extent to which they attended and responded to contextual issues, intentionally seeking to make content relevant to students, helping them build connections between their interests and the discipline, and adapting resources to create more inclusive learning environments. These differences seem to affect student performance in common exams. Our study highlights the importance of analyzing the relationships that instructors build with intention to support professional development and teacher reflection, and better understand the impact of instructors’ decisions on student performance.