Single-molecule force spectroscopy measurements of a DNA duplex comprising an artificial metal-mediated base pair are reported. The measurements reveal that DNA duplexes comprising one central imidazole:imidazole mispair rupture at lower forces than a related duplex with canonical base pairs only. In contrast, DNA duplexes with one central imidazole-Ag+-imidazole base pair (formed by the addition of Ag+ to the aforementioned duplex with the mispair) rupture at higher forces. These measurements indicate for the first time that the increase in thermal stability of a nucleic acid duplex that is observed upon the formation of a metal-mediated base pair is accompanied by a concomitant mechanical stabilization. In fact, the mechanical stabilization even exceeds the thermal one. This result indicates that nucleic acids with metal-mediated base pairs should be ideal building blocks for rigid functionalized DNA nano-objects.