<p>In cotton (<i>Gossypium hirsutum</i> L.) production, soil-borne pathogens and salinity stress are among the major environmental constraints that severely limit plant growth and productivity, particularly when they occur simultaneously. This study investigated the individual and combined effects of Verticillium wilt and salinity stress, as well as the potential of seaweed extract and arbuscular mycorrhizal fungi (AMF) to enhance stress tolerance in cotton. Under controlled conditions, the growth substrate was amended with 10% (v/v) AMF (<i>Funneliformis mosseae</i>) and a seaweed derived from <i>Ascophyllum nodosum</i>. Plants were exposed to <i>Verticillium dahliae</i> inoculation (1 × 10⁶ spores mL⁻¹) and 100 mM salinity stress under single and combined stress scenarios. Throughout the experiment, plant growth traits, physiological and biochemical indicators, ionic balance, antioxidant defense responses, mycorrhizal colonization, and rhizosphere soil properties were evaluated using an integrated approach. Combined stress conditions markedly intensified growth reductions, impaired membrane integrity, plant water status, and photosynthetic capacity, and disrupted ionic homeostasis due to excessive Na⁺ accumulation. Notably, under disease stress, biostimulant applications substantially suppressed disease severity, reducing values from nearly 60% to approximately 30%. Similarly, the pronounced effects of salinity observed under salinity and combined stress conditions were significantly alleviated by seaweed and AMF treatments. Overall, the combined application of seaweed extract and AMF emerges as an effective, environmentally friendly, and sustainable agronomic strategy to enhance cotton resilience in production systems exposed to multiple stress factors.</p>