Thermally cross-linkable photo-hydrolyzable inkjet printable polymers are used to print microfluidic channels layer-by-layer on a substrate. In one embodiment, for each layer, an inkjet head deposits droplets of a mixture of hydrophobic polymer and cross-linking agent in a pattern lying outside a two-dimensional layout of the channels, and another inkjet head deposits droplets of a mixture of poly(tetrahydropyranyl methacrylate) PTHPMA (or another hydrophobic polymer which hydrolyzes to form a hydrophilic material), cross-linking agent, and a photoacid generator (PAG) in a pattern lying inside the two-dimensional layout of the channels. After all layers are printed, flood exposure of the entire substrate to UV radiation releases acid from the PAG which hydrolyzes PTHPMA to form hydrophilic poly(methacrylic acid) PMAA, thereby rendering the PTHPMA regions hydrophilic. The layers of these now-hydrophilic patterned regions together define the microfluidic channels. The cross-linking agent (e.g., triallyl isocyanurate TAIC) forms covalent cross-links between the two polymer phases.