Organic Rankine Cycle (ORC) systems using high temperature (150–350 °C) heat resources have attracted much interest due to their high thermal efficiencies and outputs. However, the organic working fluids may react with the ORC system materials at high temperatures, which can lead to fluid decomposition, material corrosion, and other system safety problems. This study experimentally investigated the material compatibility for ORC systems with n-pentane, HFC245fa, hexamethyldisiloxane (MM), and HFE7100 as the test fluids with copper and aluminum. The results showed that HFC245fa and HFE7100 changed the hardness of copper samples by 2.22% and 5.79% and n-pentane and MM changed the tensile strength of copper samples by 0.59% and 0.66% at 250 °C for 100 h. HFC245fa also changed the hardness of aluminum samples by 3.84%, and HFE7100 changed the tensile strength of aluminum samples by 2.69%. Thus, n-pentane and MM with aluminum as materials are the better choices for high temperature ORC systems. Both copper and aluminum catalyzed n-pentane decomposition, and so copper and aluminum should be avoided in ORC systems when the heat resource temperatures are close to the fluid decomposition temperatures.