Recently, biomaterials for cartilage regeneration has been intensively investigated. However, the development of scaffolds that capture regenerated cartilage with biomechanical and structural recovery has rarely been reported. To address this challenge, platelet-rich plasma (PRP)-based cartilage constructs with a well-orchestrated symphony of cellular, biochemical and biomechanical elements were prepared by simultaneously employing chondrogenic progenitor cells (CPCs) as a cell source, optimizing platelet concentration, and adding an enzymeion activator. It was shown that this triple-optimized PRP + CPC construct possessed increased biomechanical properties and suitable biochemical signals. The following in vitro study demonstrated that the triple-optimized PRP + CPC constructs generated cartilage-like tissue with higher expression levels of chondrogenic-specific markers, more deposition of cartilage-specific extracellular matrix (ECM), and greater biomechanical values than those of the other constructs. Twelve weeks after the construct was implanted in a cartilage defect in vivo, histological analysis, qPCR, and biomechanical tests collectively showed that the triple-optimized constructs yielded a more chondrocyte-like cell phenotype with a higher synthesis of Col-II and aggrecan. More importantly, the triple-optimized constructs facilitated cartilage regeneration with better biomechanical recovery than that of the other constructs. These results demonstrate the efficacy of the triple-optimization strategy and highlight the simplicity and potency of this PRP + CPC construct for cartilage regeneration.