Presented in this paper is an innovative, uniform seismic protection system of masonry and infilled frame buildings created on the basis of a specifically upgraded sliding isolation system with new SF devices. The new building sliding-space flange protection system (BSSF system) represents a specific research segment of the integral research project, led by the fourth author, conducted in the Institute of Earthquake Engineering and Engineering Seismology (IZIIS), Ss. Cyril and Methodius University (Skopje), during three and a half years, in the frames of the innovative NATO Science for Peace and Security Project “Seismic Upgrading of Bridges in South-East Europe by Innovative Technologies (SFP: 983828)”, involving five European countries. The upgraded, seismically isolated sliding system with integrated space flange (SF) energy dissipation (ED) devices has been developed as a mechanical passive concept to provide harmonized response of building structures to strong earthquakes. It is formulated as an adaptive system, which follows the adopted concept of global optimization of seismic energy balance, through utilization of newly designed dissipation devices as a supplementary damping level to the building isolation. The new BSSF protection system is based on obligatory incorporation of the following three integrated complementary systems: (1) Sliding seismic isolation (SSI) system, (2) SF seismic energy dissipation (ED) system and (3) Earthquake displacement limiting (EDL) system. The proposed seismically resistant BSSF building system represents a qualitatively new strategy for construction of modern masonry and framed masonry buildings by applying traditional and new construction materials and providing simultaneously: (1) Full seismic safety of protected buildings, (2) Reduction of construction time, and (3) Profitable construction in seismic areas achieved by the special system characteristics.