This paper presents a method to assess the key performance indicators of aircraft designed for minimum direct operating costs and aircraft designed for minimum global warming impact. The method comprises a multidisciplinary aircraft optimization algorithm capable of changing wing, engine, and mission design variables while including constraints on flight and field performance. The presented methodology uses traditional class-I methods augmented with dedicated class-II models to increase the sensitivity of the performance indicators to relevant design variables. The global warming impact is measured through the average temperature response caused by several emission species (including carbon dioxide, nitrogen oxides, and contrail formation) over a prolonged period of 100 years. The analysis routines are verified against experimental data or higher-order methods. The design algorithm is subsequently applied to a single-aisle medium-range aircraft, demonstrating that a 57% reduction in average temperature response can be achieved as compared to an aircraft optimized for minimal operating costs. This reduction is realized by flying at 7.6 km and Mach 0.60, and by lowering the engine overall pressure ratio to approximately 37. However, to compensate for the lower productivity, it is estimated that 13% more climate-optimized aircraft have to be operated for the hypothetical fleet under consideration.