We report a directly photopatternable polythiophene derivative PToNB with o-nitrobenzyl (oNB)-functionalized side chains. PToNB has unique phototunable solubilities programmed through three stages: (i) organic-soluble/aqueous-insoluble, (ii) organic-insoluble/aqueous-insoluble, and (iii) organic-insoluble/aqueous soluble. The capability to control conjugated polymer solubility with spatiotemporal precision and orthogonal developer solvents through three stages allows for direct patterning of this conjugated polymer and provides flexibility to choose between positive and negative tone photolithography. This approach to photomodulate solubility also enables all-solution processing of multilayer stacked conjugated demonstrate here direct two-layer photopatterning with this novel conjugated polymer photoresist.