A method of sequencing a plurality of target polynucleotides arrayed on a solid support comprising: (i) incorporating one of four different nucleotides into nascent nucleic acid copy strands complementary to each of the plurality of target polynucleotides, wherein each of the four different nucleotides comprise (i) a 3'-hydroxyl protecting group, and (ii) a first reactive group coupled to a nucleobase through a cleavable linker, and where each different nucleotide of the four different nucleotides comprises a different nucleobase and a different first reactive group, wherein the first reactive group includes a first member of a pair of reactive functional groups capable of participating in a "click chemistry" reaction, a hapten, or a first oligonucleotide; (ii) sequentially forming different subsets of nucleotide-conjugate complexes, where each nucleotide-conjugate complex within each different subset of formed nucleotide-conjugate complexes is derived from only one of the different nucleotides incorporated into the nascent nucleic acid copy strands, wherein the sequential formation of each different subset of nucleotide-conjugate complexes comprises: a. introducing a conjugate comprising a detectable label and which is orthogonally reactive with only one of the four different nucleotides incorporated into the nascent nucleic acid strands, wherein the conjugate includes a second reactive group selected from a second member of the pair of reactive functional groups capable of participating in a "click chemistry" reaction, a hapten antibody, and a second oligonucleotide capable of hybridizing with the first oligonucleotide; b. detecting the formation of each nucleotide-conjugate complex within the subset by detecting the label of each introduced conjugate; c. determining a position within the solid support of each detected nucleotide-conjugate complex within the subset; and d. optionally cleaving at least a detectable label from each of the formed detectable nucleotide-conjugate complexes within the subset. (i) incorporating one of four different nucleotides into nascent nucleic acid copy strands complementary to each of the plurality of target polynucleotides, wherein each of the four different nucleotides comprise (i) a 3'-hydroxyl protecting group, and (ii) a first reactive group coupled to a nucleobase through a cleavable linker, and where each different nucleotide of the four different nucleotides comprises a different nucleobase and a different first reactive group, wherein the first reactive group includes a first member of a pair of reactive functional groups capable of participating in a "click chemistry" reaction, a hapten, or a first oligonucleotide; (ii) sequentially forming different subsets of nucleotide-conjugate complexes, where each nucleotide-conjugate complex within each different subset of formed nucleotide-conjugate complexes is derived from only one of the different nucleotides incorporated into the nascent nucleic acid copy strands, wherein the sequential formation of each different subset of nucleotide-conjugate complexes comprises: a. introducing a conjugate comprising a detectable label and which is orthogonally reactive with only one of the four different nucleotides incorporated into the nascent nucleic acid strands, wherein the conjugate includes a second reactive group selected from a second member of the pair of reactive functional groups capable of participating in a "click chemistry" reaction, a hapten antibody, and a second oligonucleotide capable of hybridizing with the first oligonucleotide; b. detecting the formation of each nucleotide-conjugate complex within the subset by detecting the label of each introduced conjugate; c. determining a position within the solid support of each detected nucleotide-conjugate complex within the subset; and d. optionally cleaving at least a detectable label from each of the formed detectable nucleotide-conjugate complexes within the subset. a. introducing a conjugate comprising a detectable label and which is orthogonally reactive with only one of the four different nucleotides incorporated into the nascent nucleic acid strands, wherein the conjugate includes a second reactive group selected from a second member of the pair of reactive functional groups capable of participating in a "click chemistry" reaction, a hapten antibody, and a second oligonucleotide capable of hybridizing with the first oligonucleotide; b. detecting the formation of each nucleotide-conjugate complex within the subset by detecting the label of each introduced conjugate; c. determining a position within the solid support of each detected nucleotide-conjugate complex within the subset; and d. optionally cleaving at least a detectable label from each of the formed detectable nucleotide-conjugate complexes within the subset.