Two different online homework systems were administered to students in a first-quarter general chemistry course. This study used a multiple regression model to control for the students' academic and socioeconomic background, and it was found that students who completed the online homework activities performed significantly better on a common comprehensive final exam than students who did not participate. More specifically, it was found that students who completed a precourse assignment on an adaptive-responsive homework system (ALEKS; Assessment and Learning in Knowledge Spaces) could expect on average their final exam score to increase by over 13 points when compared to nonparticipating students. Students who completed a precourse assignment on a traditional responsive homework system (MasteringChemistry) also saw an average increase in their final exam score by roughly 8 points versus those who did not participate. Students who worked on the online homework for the entire quarter saw even greater gains in their final exam scores compared to nonparticipants. These findings suggest responsive online homework in general, and a responsive-adaptive learning system driven by knowledge space theory in particular, has a significant positive impact on student performance in the first-quarter general chemistry course.