New materials are traditionally developed using costly and time-consuming trial and error experimental efforts. This is followed by an even lengthier material-certification process. Consequently, it takes 10–20 years before a newly discovered material is commercially employed. An alternative approach to the development of new materials is the so-called materials-by-design approach within which a material is treated as a complex system and its design and optimization is carried out by employing computer-aided engineering analyses, predictive tools and available material databases. In the present work, the materials-by-design approach is utilized to redesign a grade of high-strength low-alloy steels with improved mechanical properties (primarily strength and fracture toughness), processability (e.g. castability, hot formability and weldability) and corrosion resistance. Toward that end, a number of material thermodynamics, kinetics of phase transformations, and physics of deformation and fracture computational models and databases have been developed/assembled and utilized within a multidisciplinary, two-level material-by-design optimization scheme. To validate the models, their prediction is compared against the experimental results for the related steel high-strength low-alloy 100. Then the optimization procedure is employed to determine the optimal chemical composition and the tempering schedule for a newly designed high-strength low-alloy steel grade with enhanced mechanical properties, processability and corrosion resistance.