Mineral weathering is a balanced interplay among physical, chemical, and biological processes. Fundamental knowledge gaps exist in characterizing the biogeochemical mechanisms that transform microbe-mineral interfaces at submicron scales, particularly in complex field systems. Our objective was to develop methods targeting the nanoscale by using high-resolution microscopy to assess biological and geochemical drivers of weathering in natural settings. Basalt, granite, and quartz (53-250 µm) were deployed in surface soils (10 cm) of three ecosystems (semiarid, subhumid, humid) for one year. We successfully developed a reference grid method to analyze individual grains using: (1) helium ion microscopy to capture micron to sub-nanometer imagery of mineral-organic interactions; and (2) scanning electron microscopy to quantify elemental distribution on the same surfaces via element mapping and point analyses. We detected locations of biomechanical weathering, secondary mineral precipitation, biofilm formation, and grain coatings across the three contrasting climates. To our knowledge, this is the first time these coupled microscopy techniques were applied in the earth and ecosystem sciences to assess microbe-mineral interfaces and in situ biological contributors to incipient weathering.