Abstract Metal ion interactions with DNA have far-reaching implications in biochemistry and DNA nanotechnology. Ag + is uniquely interesting because it binds exclusively to the bases rather than the backbone of DNA, without the toxicity of Hg 2+ . In contrast to prior studies of Ag + incorporation into double-stranded DNA, we remove the constraints of Watson-Crick pairing by focusing on homo-base DNA oligomers of the canonical bases. High resolution electro-spray ionization mass spectrometry reveals an unanticipated Ag + -mediated pairing of guanine homo-base strands, with higher stability than canonical guanine-cytosine pairing. By exploring unrestricted binding geometries, quantum chemical calculations find that Ag + bridges between non-canonical sites on guanine bases. Circular dichroism spectroscopy shows that the Ag + -mediated structuring of guanine homobase strands persists to at least 90 °C under conditions for which canonical guanine-cytosine duplexes melt below 20 °C. These findings are promising for DNA nanotechnology and metal-ion based biomedical science.