We investigate here the thickness effect on microstructures and mechanical properties of a quenched and tempered 178 mm thickness ASTM A517 GrQ steel. The microstructures at sub-surface, 1/4 thickness (t/4), and 1/2 thickness (t/2) were characterized. A comparison of hardness, strength, and impact toughness of the different positions shows that the lowest strength and toughness occurred at t/2, where a mixture of coarse, tempered martensite and bainite were found, and their inter-lath boundaries were occupied with highly dense, film-like or coarse, spheroidized carbides. The cooling rate for transformation was measured to be 0.6 °C/s at t/2 from the industrial processing data. In addition, the alloy elements at t/2 were heavily segregated, as revealed by electron probe microanalysis (EPMA) and a microhardness test. The resulted coarse microstructures thus lowered both the yield strength and the impact energies significantly, e.g., the crack propagation energy was completely lost at −60 °C. This study correlates the variation of mechanical properties to varied transformed microstructures based on the industrial quenching condition, which shows promise for improving the designing of the hardenability and controlling the carbides for ultra-thick quenched and tempered steel.