Zeotropic refrigerant mixtures receive increased attention for industrial heat pump applications with heat sink temperatures in the range of 80 to 200 °C. The temperature glide of zeotropic mixtures can match the large temperature changes of heat source and sink as typical for industrial processes. Significant COP improvements were experimentally proven in prior work for operating conditions where the heat source and heat sink had equal temperature changes of 25 K or 35 K. The performance of mixtures over pure refrigerants for applications with different temperature changes on the heat sink and source is rarely experimentally and systematically investigated. This study conducts tests at all combinations of 5 K, 15 K, and 25 K temperature changes for the heat source and sink on a laboratory-scale HTHP at a heat source inlet temperature of 60 °C and a heat sink outlet temperature of 100 °C. Pure R1224yd(Z) is compared against a mixture of R1224yd(Z) with R1234yf (75%/25% by mass), featuring a temperature glide of 15 K at a dew point temperature of 60 °C. The experiments show that the mixture is more robust against varying operating conditions, i.e., the mixture maintains the COP higher over 7 out of 9 operating conditions. Future work will focus on verifying a suitable model and supporting the results with studies for natural refrigerants.