Differences in simulations of tropical marine low-cloud cover (LCC) feedback are sources of significant spread in temperature responses of climate models to anthropogenic forcing. Here we show that in models the feedback is mainly driven by three large-scale changes—a strengthening tropical inversion, increasing surface latent heat flux, and an increasing vertical moisture gradient. Variations in the LCC response to these changes alone account for most of the spread in model-projected 21st century LCC changes. A methodology is devised to constrain the LCC response observationally using sea surface temperature (SST) as a surrogate for the latent heat flux and moisture gradient. In models where the current climate’s LCC sensitivities to inversion strength and SST variations are consistent with observed, LCC decreases systematically, which would increase absorption of solar radiation. These results support a positive LCC feedback. Correcting biases in the sensitivities will be an important step toward more credible simulation of cloud feedbacks.