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Summary The air-stable layered semiconductor Bi2O2Se has recently attracted extensive interest because of its potential application in electronics, optoelectronics, ferroelectrics, and thermoelectrics. For many of these applications, thermal transport in Bi2O2Se is of great importance, but a complete understanding of the process remains elusive. Here, we perform a combined experimental and theoretical study of the anisotropic thermal conductivity of single-crystalline Bi2O2Se in comparison with Bi2Se3. Bi2O2Se exhibits relatively higher through-plane thermal conductivity but lower in-plane thermal conductivity, resulting in substantially smaller thermal anisotropy. This behavior originates from the stronger interlayer electrostatic interaction in Bi2O2Se compared with the typical van der Waals coupling in layered materials, making the phonon isoenergy surfaces less anisotropic and, thus, weakening phonon focusing in the in-plane directions. Our study advances the fundamental understanding of thermal anisotropy in layered materials with various interlayer interactions and will facilitate application of Bi2O2Se in electronics and thermoelectrics.