The present disclosure describes methods which employ a patterning photolithography/etch operations to form self-aligned interconnects with multi-metal gap fill. For example, the method includes a first pattern structure and a second pattern structure formed over a dielectric layer. Each of the first and second pattern structures includes a pair of spacers, and a center portion between the pair of spacers. A first opening, self-aligned to a space between the first and second pattern structures, is formed in the dielectric layer. A first conductive material is deposited in the first opening. The center portion of the second pattern structure is removed to form a void above the dielectric layer and between the pair of spacers of the second pattern structure. A second opening, self-aligned to the void, is formed in the dielectric layer; and a second conductive material is deposited in the second opening.