The synthesis of poly(urethane-urea) (PUUs) bearing deactivated diamines within the backbone polymer chain is presented. Several deactivated diamines present interesting properties for several applications in the biomaterial field due to their attractive biocompatibility. Through an activation with Chloro-(trimethyl)silane (Cl-TMS) during the polymerization reaction, the reactivity of these diamines against diisocyanates was triggered, leading to PUUs with high performance. Indeed, through this activation protocol, the obtained molecular weights and mechanical features increased considerably respect to PUUs prepared following the standard conditions. In addition, to demonstrate the feasibility and versatility of this synthetic approach, diisocyanate with different reactivity were also addressed. The experimental work is supported by calculations of the electronic parameters of diisocyanate and diamines, using quantum mechanical methods.