<p>Hydroponic horticulture will play a key role in future food production as the growing global population becomes increasingly urbanised. Tomato (<i>Solanum lycopersicum</i>) is a widely grown and consumed crop that is already cultivated hydroponically in glasshouses in areas of the world with cooler climates, such as Northern Europe. Hydroponic growing systems enable high yields but can enhance disease susceptibility which increases the risk of devastating yield losses. Manipulation of the hydroponic microbiome has been proposed as a strategy to protect plants against disease. However, this hypothesis remains largely untested. We examined whether introducing synthetic communities of plant-beneficial microbes (SynComs) could offer a sustainable disease protection solution for hydroponic tomato production. We identified individual microbes and in turn two SynComs that induce systemic disease resistance during the vulnerable early stages of development. The two SynComs were evaluated further in a commercial-scale greenhouse trial. Although both SynComs reduced early growth, they had no adverse effects on yield or fruit quality. Strikingly, while only one SynCom strain consistently persisted in the hydroponic stone wool substrate throughout the six-month trial, the introduction of disease-suppressive SynComs at sowing had significant and similar impacts on bacterial community structure six months later. Our findings demonstrate that microbial SynComs can reduce disease susceptibility of hydroponically grown tomato without compromising yield, offering a viable and sustainable approach for crop protection in controlled environment agriculture.</p>