A major challenge in paleoclimatology is disagreement between data and models for periods of warm climate. Data generally indicate equable conditions and reduced latitudinal temperature gradients, while models generally produce colder conditions and steeper latitudinal gradients except when using very high CO2. Here we show congruence between temperature indicators and climate model output for the cool greenhouse interval of the latest Cretaceous (Maastrichtian) using a global database of terrestrial and marine indicators and fully coupled simulations with the Community Climate System Model version 3. In these simulations we explore potential roles of greenhouse gases and properties of pre-anthropogenic liquid clouds in creating warm conditions. Our model simulations successfully reproduce warm polar temperatures and the latitudinal temperature gradient without overheating the tropics. Best fits for mean annual temperature are simulations that use 6× preindustrial levels of atmospheric CO2, or 2× preindustrial levels of atmospheric CO2 and liquid cloud properties that may reflect pre-anthropogenic levels of cloud condensation nuclei. The Siberian interior is problematic, but this may relate to reconstructed elevation and the presence of lakes. Data and models together indicate tropical sea-surface temperatures ∼5 °C above modern, an equator-to-pole temperature difference of 25–30 °C, and a mid-latitudinal temperature gradient of ∼0.4 °C per 1° latitude, similar to the Eocene. Modified liquid cloud properties allow successful simulation of Maastrichtian climate at the relatively low levels of atmospheric CO2 indicated by proxies and carbon cycle modeling. This supports the suggestion that altered properties of liquid clouds may be an important mechanism of warming during past greenhouse intervals.