To study the effect of urban building layout on energy consumption and to identify the key layout parameters, the simulation experiment and the sensitivity analysis method are used to simulate 200 kinds of layout in Wuhan from the perspective of reducing the solar radiation and heat gain. Firstly, the parameter combinations are created by Latin hypercube sampling (LHS). Then, 200 energy consumption models are established and calculated by R language and EnergyPlus energy consumption simulation software. Finally, the standard regression coefficient (SRC) and treed Gaussian process (TGP) global sensitivity analysis methods are implemented in order to explore the influence of the nine layout parameters of both horizontal and vertical direction on the target building energy consumption. The results show that the building layout has a significant effect on the energy consumption, the changes of 9 layout parameters would cause fluctuations in cooling, heating and total energy consumption of 15.8%, 26.8%, and 4.4%, respectively. The two sensitivity analysis results are similar. The parameter that has the greatest influence on the cooling and total energy consumption is the height of building in the western part, whose main effects are around 0.3. The least influential parameter is the width of the south, whose main effects are bellow 0.1. The dominant parameter of heating energy is the height of the south building, which can account for more than 30% of the variations of the output, and the smallest is the east building width. When the parameter value is much larger than the target building size, the influence of each parameter on energy consumption is reduced, and using the TGP sensitivity analysis is more reasonable. From the perspective of energy-saving and emissions reduction, this paper can provide theoretical basis for the urban planning and building layout.