A series of seven mixed-ligand coordination polymers, namely {[Cd₄(H₂L1)₄(suc)₄]·3H₂O}_n (1), {[Cd₄(H₂L1)₃(suc)₄]·5H₂O}_n (2), {[Cd₂(HL1)₂(suc)]·8H₂O}_n (3), {[Cd(H₂L2)(suc)]·3H₂O}_n (4), {[Cd(H₂L3)(suc)]·3H₂O}_n (5), {[Co(H₂L1)(chdc)(H₂O)]·H₂O}_n (6), {[Co(H₂L2)(chdc)(H₂O)]}_n (7) have been produced by the reaction of three 2-amino-4,6-dipyridylpyrimidine isomers (H₂L1, H₂L2, H₂L3) and secondary ligand 1,4-succinic acid (H₂suc) or 1,4-cyclohexanedicarboxylic acid (H₂chdc) with Cd(II) and Co(II) salts under hydrothermal conditions. All these compounds have been structurally determined by elemental analysis, IR and single-crystal X-ray diffraction. The three isomers are introduced in a mixed-ligand system for the first time. For the H₂L1–H₂suc–Cd(II) system, it is found that the structures of compounds 1–3 exhibiting a 1-D double-chain, a rare 1-D quadruple nano-chain and a 2-D network with (6,3) topology, respectively, are influenced by the ratio of metal-to-ligand. When H₂L2 and H₂L3 were used instead of H₂L1, two 1-D chains (compounds 4 and 5) were obtained. Although they have the same molecular formula and structure motif, their supramolecular networks constructed by hydrogen-bondings and π–π stacking interactions are different. When H₂L1 and H₂L2 were introduced into the Co(NO₃)₂–H₂chdc system, compounds 6 and 7 were successfully isolated, and display a zigzag chain and a helical chain, respectively. Interestingly, the cis- and trans-conformations of H₂chdc were separated completely in the two compounds. The results reveal that both the coordination structure and the supramolecular assembly could be directed by the ligand isomers. Furthermore, several intriguing water clusters have been observed in these mixed-ligand compounds, such as a novel (H₂O)₁₀cluster in 2, a 2-D water net formed by (H₂O)₈clusters in 3, a 1-D undulated water chain in 4 and a chair-shaped (H₂O)₆cluster in 5. The solid-state properties of compounds 1–7 such as thermal stability and fluorescence have also been investigated.