Loess’s permeability properties increase under alternating wet and dry conditions, a phenomenon that is closely related to the soil’s pore structure. Among the pore structure properties, spatial topology is important. To further investigate the relationship between loess’s spatial topography and its infiltration properties under alternating wet and dry conditions, loess with different water contents is scanned by an industrial computed tomography (CT) scanner, and single-phase seepage simulations are performed. The results show that the diameters of the connected pore spaces increase along with water content; the pore throat length is positively correlated with the water content, reaching a maximum of 753.32 μm; and greater water contents result in stronger pore connectivity and larger increases of connected pore space coordination numbers. The results of the permeability simulation show that increases in connected pores, pore throat lengths, and coordination numbers lead to increased permeability, and the correlation is strongest between the coordination number and permeability. It is important to study the relationship between spatial topology and loess permeability for practical engineering applications.