Collaboration is an important career skill and vital to student understanding of the social aspects of science, but less is known about relationships among collaborative-learning strategies, classroom climate, and student learning. We sought to increase the collaborative character of introductory undergraduate laboratory classrooms by analyzing a 9-week intervention in 10 classrooms (n = 251) that participated in cooperative-learning modules (promoting interdependence via a modified jigsaw technique). Students in an additional 10 classrooms (n = 232) completed the same material in an unstructured format representative of common educational practice. Results showed that, when between-class variance was controlled for, intervention students did not score higher on weekly quizzes, but science interest and prior science experience had a reduced relationship to quiz performance in intervention classrooms. Also, intervention classrooms showed increased collaborative engagement at both whole-class and individual levels (24 students at three time points), but the intervention was only one of several factors found to account for late-intervention classroom collaborative engagement (prosocial behavior and discussion practices). Taken together, findings suggest that integrating interdependence-based tasks may foster collaborative engagement at both small-group and whole-classroom levels, but by itself may not be enough to promote increased student achievement.