A laser direct writing technique was used successfully to carry out subsurface micromachining of three-dimensional microfluidic structures. It involves simple steps of femtosecond laser irradiation to project a latent image of channels or chambers of various dimensions into a photosensitive Foturan glass, thermal annealing to produce crystallites of lithium metasilicates in the laser-irradiated regions, and use of a diluted hydrofluoric acid solution to remove the crystallized structures through selective chemical etching. The etched surfaces may be smoothened significantly through a secondary thermal annealing process. A microfluidic reagent mixer and reactor consisting of four cubic chambers and multiple channels was produced inside a single piece of glass to demonstrate that the technique can be used for rapid device fabrication without recourse to the cumbersome and expensive processes of alignment, stacking, bonding or assembly of the individual microcomponents. The direct writing technique makes it easy to integrate micro–optical and microfluidic components into a single chip.