Background <p>Lead (Pb) is a highly toxic non-essential element, whose toxicity has been documented globally due to its disruption of critical plant functions and its effect on overall yield, ultimately entering the food chain. Beneficial microbes such as <i>Trichoderma</i> sp. play a pivotal role in promoting plant growth, especially under heavy metal stress.</p> Results <p>In this study, a novel fungal bio-inoculant, <i>Trichoderma harzianum</i> isolate Zag-1, was utilized both in vitro and in a pot experiment to alleviate Pb-induced stress. According to in vitro preliminary findings, <i>T. harzianum</i> Zag-1 could tolerate Pb (II) up to 1500 ppm on potato dextrose broth (PDB) medium and had a maximum removal efficiency of 70.40% at 500 ppm. Alongside, <i>T. harzianum</i> was used to improve the growth of maize plants at two levels (low: 500 ppm and high: 1000 ppm), and the results indicate that both levels negatively affect its growth and physiological traits. Exposure to 1000 ppm Pb severely inhibited maize development, resulting in reductions in shoot height (13.04%), root length (28.17%), shoot and root fresh weights (Fwt) (34.03% and 20.74%), and dry weights (Dwt) (41.79% and 15.15%), respectively, as compared to the controls. Furthermore, Pb (II) stress at 1000 ppm significantly depleted photosynthetic pigments (chlorophyll a, Chl b, carotenoids, and total pigments reduced by 52.33%, 47.37%, 58.62%, and 52.75%, respectively) and impaired water status, causing a 27.26% reduction in relative water content (RWC) in comparison to non-stressed plants. Furthermore, in Pb-stressed plants (1000 ppm), oxidative stress markers including membrane leakage (ML), malondialdehyde (MDA), and hydrogen peroxide (H₂O₂) were increased significantly by 148.58%, 105.31%, and 50.03%, respectively, as compared to non-stressed control plants. However, the inoculation of plants with <i>T. harzianum</i> Zag-1 increased Fwt (17.96%) and Dwt (17.00%) of biomass, Chl a (69.77%), Chl b (52.63%), RWC (2.84%), and membrane stability index (MSI, 10.89%) in comparison to their control counterparts. <i>T. harzianum-</i>inoculated plants had 12.36%, 45.65%, 37.65%, and 4.56% higher soluble protein, proline, carbohydrates, and glycine betaine concentrations, respectively, than non-inoculated controls at 1000 ppm of Pb. However, at 1000 ppm Pb, ML, MDA, and H₂O₂ contents decreased by 23.59%, 40.36%, and 25.41%, respectively, compared to <i>T. harzianum</i>-free plants. Results on antioxidants showed that <i>T. harzianum</i> inoculation led to a significant rise in enzyme activities (10.36, 29.22, and 8.44%, for peroxidase [POD], polyphenol oxidase [PPO], and ascorbate peroxidase [APX], respectively) in plants treated with 1000 ppm of Pb.</p> Conclusion <p>Remarkably, the locally isolated <i>T. harzianum</i> strain Zag-1 demonstrates a distinct and enhanced tolerance to Pb stress, coupled with a superior ability to modulate antioxidant defense, ionic homeostasis, and metabolic adjustments of maize plants under Pb stress, presenting a valuable tool for promoting climate-resilient farming in Pb-affected areas.</p>