The biogenesis of silver nanoparticles by fungi is an ecologically clean and nontoxic method compared to other physical and chemical methods. Thus, we aimed to discuss the mycosynthesis of extracellular size-controlled AgNPs. After comprehensive screening, Aspergillus fumigatus BTCB10 (KY486782) was selected for the synthesis of AgNPs of controlled size. Characterization was performed by UV-Vis spectrophotometer, Zetasizer, X-Ray Diffraction (XRD), FTIR (Fourier-transform infrared), Atomic Force Microscopy (AFM), and Scanning Electron Microscopy (SEM) along with functional assays—antibacterial and MTT assays. Data suggested that under optimized conditions, i.e., temperature 25°C, AgNO3 concentration 1 mM, biomass 7 g, fungal culture age 7 days, pH 6, ratio of cell-free filtrate (CFF)/silver nitrate (3 : 2), NaCl 20%, and under dark light, the smallest size AgNPs of 0.681 nm with 100% monodispersity was obtained as evident by a zeta potential of -23.4 mV, UV-Vis band at 400 nm, and the presence of O-H and C=O groups confirmed by ATR-FTIR; XRD revealed the crystalline nature of AgNPs; additionally, cube-shaped AgNPs were revealed by Scanning Electron Microscopy (SEM). Moreover, synthesized AgNPs exhibited antibacterial activity against multidrug-resistant bacterial strains, notably, Klebsiella pneumoniae BTCB04, Acinetobacter BTCB05, Pseudomonas aeruginosa BTCB01, and Escherichia coli BTCB03, while maximum 7-fold was observed with Acinetobacter BTCB05. AgNPs demonstrated no cytotoxic activity against HepG2 cells; however, in combination with cisplatin, antiproliferative and cytotoxic effects became more evident and significant in comparison to control and as single agent. Taken together, the data suggested that economical and smallest size AgNPs can be biosynthesized from Aspergillus fumigatus BTCB10 and be used as antibacterial and antiproliferative agents in combination with current drugs against clinically relevant multiple drug-resistant bacterial and tumoral cells. Further studies are required to confirm their effects employing in vivo disease models.