A layered quaternary uranium-containing oxide, Cs2Mn3U6O22, was crystallized from a cesium chloride flux. The crystal structure was determined to consist of α-U3O8 topological layers that are separated by alternating cesium and manganese layers. This ordered arrangement creates a separation between manganese layers of 13 Å, leading to complex low-dimensional magnetic properties. The compound crystallizes in a new structure type in the monoclinic space group, C2/m, with a = 6.8730(10) Å, b = 11.7717(17) Å, c = 13.374(2) Å, and β = 99.673(5)°. The magnetic properties were measured and analyzed by first-principles density functional theory calculations.