A polyurethane (PU) foam nanocomposite impregnated with iron oxide nanoparticles (IONPs) was developed to remove arsenic (As) from drinking water at ppb concentrations. The effect of synthesis and application parameters such as the size of IONPs, pH levels, weight of adsorbents, and arsenic concentrations on the performance of PU-IONP adsorbents in removing arsenic were studied. The prepared adsorbents were characterized by scanning electron microscopy and energy dispersive X-ray microscopy to evaluate the microstructure of PU-IONPs and the surface adsorption of arsenic species, respectively. Atomic absorption spectrometry was conducted to measure the concentration of arsenic in the treated solutions in order to calculate the removal capacity of PU-IONPs. The experimental results revealed that decreasing the size of IONPs from 50–100 nm to 15–20 nm yields a higher removal capacity. Increasing the weight of the used adsorbents and the contact time led to an increase in the removal capacity as well. As the arsenic species (III and V) concentration increased in the solution, the removal capacity of PU-IONPs decreased. In a column study, a long-term cyclic operation mode was found to be very effective in removing arsenic; 100% removal capacity was achieved when 500 ml of As solution (100 ppb) was treated.