Achieving the correct sulfate balance in limestone calcined clay cements (LC3) to control aluminate hydration is critical for early hydration and property development, but the role of the calcined kaolin (metakaolin) fraction relative to other compositional variables has not been previously well-explored. In addition, little published research has investigated the influence of water-to-solid ratio (w/s) and superplasticizers in this context. This study assesses the influence and quantifies the relative significance of compositional predictors on the sulfate balance and cumulative heat evolved by 24 h for LC3 through a stepwise regression model. Sulfate balance was defined as the time difference between the sulfate depletion point and the time of maximum of alite peak obtained from a time derivative of data obtained through isothermal calorimetry. A methodology based on Kernel smoothing was used to precisely identify these events. The first 24 h of hydration of some LC3 pastes was also monitored via in-situ X-ray diffraction to develop linkages between LC3 composition and hydrated phase assemblage. The statistical analysis identified the metakaolin fraction as particularly significant for the sulfate balance. The results suggest that the metakaolin fraction influences the sulfate balance of LC3 both directly and through its interactions with other constituent materials such as limestone.