Recent advances in alternative water desalination technologies have become increasingly common, due in part to expanding water scarcity and the ability to deliver usable water without the high energy cost and advanced infrastructure required of traditional desalination technologies such as reverse osmosis (RO). One such emerging technology is iron-based desalination or the use of nano- (or micron-sized) metals (principally iron) to desalinate water. In this study, iron-based desalination was coupled with passive sulfate reduction technology (SRB) to partially treat saline irrigation water similar in composition to that encountered in the San Joaquin Valley, California, USA. Water scarcity, especially in the southwestern United States, is driving an effort to identify and use less expensive but effective desalination methods to allow the use of saline groundwater, seawater, and impounded saline agricultural drainage and runoff for crop growth. The system described here used a synthetic water mimicking a typical saline irrigation water; this was then routed through a sulfate-reducing bioreactor to remove the sulfate prior to entry into an N-ZVM reactor for removal of Na and Cl. Sulfate at high concentrations can inhibit Na and Cl removal in N-ZVM reactors. The results showed that the sulfate was reduced from 2500 mg/L to less than 250 mg/L in the bioreactor, which allowed the N-ZVM to reduce the Na and Cl by 50%. This allowed the conductivity to decrease from 9.2 mS to about 5 mS. Synthetic irrigation water without sulfate removal was only desalinated by about 10%. The observed change in conductivity, sodium, and chloride content allowed the discharged water to be used for irrigation of many field crops and some vegetables. This paper provides reactor development, manufacture, and performance information including recommendations for continued performance increases.