A water-enabled visual detection strategy has been developed for the sequence-specific identification of target DNA. The conceptual basis of the assay scheme, water condensation, is environmentally friendly and chemical transformation-free, thus offering significant assay advantages over conventional diagnostic systems. This label-free strategy operates on a target-driven generation of a hydrophilic structure and alteration of surface wettability and, consequently, transition of morphological state of and light propagation mode in the surface-condensed water. The chip array detection system, implemented herein with the ligase chain reaction-rolling circle amplification protocol, has allowed the achievement of high sensitivity (600 copies), high selectivity (single-base discrimination specificity), and multiplexed analysis capability.