Heavy metals in landfill leachate are easily adsorbed by soil particles, causing serious threats to human health and surrounding environments. Mining and metallurgy activities are intensive in Northwest China, thereby enlarging threats. The aim of the present study is to enhance our knowledge about the linkage between the microstructural evolution of the loess soil induced by lead contamination and the macro air and liquid permeability properties. A series of air and liquid permeability tests on the uncontaminated and Pb-contaminated loess specimens were conducted. Their air and liquid permeability properties were evaluated on the basis of Darcy’s law and the soil–water retention curves, respectively. The microstructural evolution, when subjected to low and high Pb2+ concentrations, was assessed using scanning electron microscopy (SEM), X-ray diffraction (XRD), mercury intrusion porosimetry (MIP), and zeta potential tests. The intrusion of Pb2+ decreases the absolute zeta potential ζ, which in turn leads to a more distinct agglomerated structure and higher intrinsic permeability. Moreover, the dedolomitization and associated cerussite (PbCO3) precipitation are deemed as the main cause of micropore clogging, whereas the corrosion of the cement between soil particles by H+ shows a good correspondence to an increase in the number of mesopores. With the concentration of Pb2+ increasing from 0 to 2,000 mg/kg, the proportion of micropores decreases from 37.9% to 15.1%, and the proportion of mesopores increases from 17.3% to 53.3%. In addition, the air entry value decreased from 19.5 to 12.8 kPa, indicating that the water retention behavior decreased. The findings highlight the impacts of lead contamination on the microstructure and macro permeability properties and give some design guideposts to heavy metal-contaminated site remediation.