Neuroscience research has produced tremendous insight into how the human brain supports learning and social interactions. Still, laboratory-generated findings do not straightforwardly generalize to real-world environments: Previous studies have typically measured single individuals or one-on-one interactions, in highly controlled laboratory settings. By contrast, in our work, we gauged dynamic social interactions in a complex real-world group setting outside of the laboratory, shedding light on the role of brain synchrony in a more natural environment. Concretely, we partnered with two New York City high schools, and followed groups of high school students and their teacher throughout the school year, recording their brain activity during their regular biology classes using portable electroencephalogram (EEG) technology. We found that the extent to which students’ brainwaves were in sync with each other and with the teacher was correlated with students’ personalities (specifically, their attitude toward group activities), their social closeness to the teacher and their peers, how engaged they were on a given day, and how engaging the class content was. Further, brain synchrony between students increased if they had interacted with each other face-to-face prior to class. In sum, brain-to-brain synchrony predicted how much students liked class and each other. With this work, we hope to offer a promising new method to investigate the neuroscience of group interactions—research that can shed light on the dynamics of the workplace or the family unit. More concretely and immediately, our findings suggest that face-to-face interaction and engaging content are important for learning and social cohesion.