While it is well-known that cool roofs can efficiently reduce cooling demand in buildings, their overall energy performance in mixed and cold climates has been a topic of debate. This paper presents a comprehensive simulation study to evaluate the combined impact of roof reflectivity, insulation level, and construction type (adhered vs attached) on annual energy demand and energy costs in the United States, for different buildings and climate zones. EnergyPlus was used to model three building types (retail, office, and school buildings) for the 16 most climate-representative locations in the US using typical reflectivity and insulation values. The results show that (i) roof reflectivity is equally important to roof insulation in warm climates; (ii) for low-rise offices and schools, the benefits of reflective roofs vs dark-colored roofs are clear for all US climatic zones, with higher savings in warm climates; (iii) for big-box-retail buildings, reflective roofs perform better except for cold climate zones 7–8; (iv) dark-colored, mechanically attached roofs achieve slightly better performance than reflective roofs in mixed and cold climates. Decision makers should consider building type, climatic conditions, roof insulation levels, and durability performance, along with roof reflectivity, when assessing the overall potential benefits of cool roofs.