This work deals with the design of a fusion reactor first-wall material, taking into account both low-activation and thermal-mechanical properties. The concept of “low activation” is discussed in detail, and a new definition is proposed that takes into account not only waste-related problems, but also maintenance and accident scenarios. The results of a thermal-mechanical analysis of some proposed materials, performed in a demonstration reactor under operating conditions, are presented. Among the austenitic stainless steels, VA64 has proved to be the most effective material as far as thermal stress is concerned. The maximum von Mises tensile stress is below the elastic limit. The radioactivity induced in VA64 alloy is analyzed. The long-term activity does not satisfy the stated limits. Therefore, the technique of elemental substitution in steels is tackled. A low-activation version of VA64 (named VA64LA) is proposed that is formed by removing the niobium content and replacing it with titanium. This new alloy has been analyzed with regard to each characteristic required for a first-wall material, and it has proved to be a promising austenitic steel for fusion reactor application.