Two-layer single phase flow microchannels were studied for cooling of electronic chips with a hot spot. A chip with 2.45 × 2.45 mm footprint and a hot spot of 0.5 × 0.5 mm in its center was studied in this research. Two different cases were simulated in which heat fluxes of 1500 W cm−2 and 2000 W cm−2 were applied at the hot spot. Heat flux of 1000 W cm−2 was applied on the rest of the chip. Each microchannel layer had 20 channels with an aspect ratio of 4:1. Direction of the second microchannel layer was rotated 90 deg with respect to the first layer. Fully three-dimensional (3D) conjugate heat transfer analysis was performed to study the heat removal capacity of the proposed two-layer microchannel cooling design for high heat flux chips. In the next step, a linear stress analysis was performed to investigate the effects of thermal stresses applied to the microchannel cooling design due to variations of temperature field. Results showed that two-layer microchannel configuration was capable of removing heat from high heat flux chips with a hot spot.