The performances of various transverse-flow double-layer microchannel heat sink configurations were evaluated compared to those of parallel-flow heat sink configurations via conjugate heat transfer analysis. For the analysis, three-dimensional Navier–Stokes and energy equations for steady incompressible laminar flow were solved using a finite-volume solver. Water with temperature-dependent thermophysical properties was used as a coolant. The thermal resistances were evaluated for various flow configurations of both cross-channel and parallel-channel designs with identical geometric parameters and total flow rate. Changes in the microchannel flow direction lead to remarkable changes in thermal resistance and temperature uniformity. A transverse-flow configuration exhibited the best overall performance among the tested flow configurations in terms of the thermal resistance, temperature uniformity, and pressure drop.