Polyisoprene is the most important composition of natural rubber. The green catalytic polymerization of isoprene by earth-abundant metal iron is a promising next-generation manufacturing process in the rubber industry. We now show that a series of unsymmetrical phosphinoquinoline Fe(II) precatalysts can efficiently catalyze isoprene polymerization, producing polyisoprene elastomers with controlled microstructures. The structures of these designed Fe(II) complexes were well-defined by NMR spectra and X-ray single crystal diffraction analysis. Activation with only 5 equiv of dMAO (dry methylaluminoxane) enabled the phosphinoquinoline Fe(II) complexes to catalyze isoprene polymerization with remarkable activity (up to 3431 kgPI·molFe–1·h–1), yielding polyisoprene with a predominantly cis-1,4/3,4 mixed microstructure (ca. 1:1 ratio). The bidentate N,P-ligands, containing strongly coordinating phosphorus atoms, effectively stabilized the iron active centers, offering high monomer conversion and polyisoprene with high molecular weight at approximately 105 Da across a broad temperature range (−10 to 100 °C). Control over polymerization activity and polyisoprene microstructure was achieved by modifying the ligand structures. Aryl-substituted catalysts exhibited high activity (409 kgPI·molFe–1·h–1) and excellent cis-1,4 stereoselectivity (cis-1,4/trans-1,4 > 97:1), highlighting the synergistic effects of ligand electronic and steric properties on catalytic performance and the isoprene coordination–insertion polymerization mechanism.