An uncertainty assessment framework based on Karhunen–Loevè expansion (KLE) and probabilistic collocation method (PCM) was introduced to deal with flood inundation modeling under uncertainty. The Manning's roughness for channel and floodplain were treated as 1D and 2D, respectively, and decomposed by KLE. The maximum flow depths were decomposed by the 2nd-order PCM. Through a flood modeling case with steady inflow hydrographs based on five designed testing scenarios, the applicability of KLE-PCM was demonstrated. The study results showed that the Manning's roughness assumed as a 1D/2D random field could efficiently alleviate the burden of random dimensionality within the analysis framework, and the introduced method could significantly reduce repetitive runs of the physical model as required in the traditional Monte Carlo simulation (MCS). The study sheds some light on reducing the computational burden associated with flood modeling under uncertainty which is useful for the related damage quantification and risk management.