Tylenchulus semipenetrans, the causal agent of the ‘citrus slow decline’, is considered to be the most devastating nematode pest of citrus, causing considerable crop losses throughout the world. The management of this citrus nematode represents a significant challenge due to its wide host range and its adaptability to various environmental conditions. Nematicides application is the most prevalent control approach, however, their use often is associated with increased production costs and major risks to consumer health and the environment. The objective of this study is to contribute to the development of an alternative and effective method to control this plant-parasite. It intends to evaluate the resistance of the seven commonly used citrus rootstocks in Morocco based on their agronomic, physiological, and biochemical behavior in response to inoculation with T. semipenetrans. Results indicated that T. semipenetrans exhibited a strong reproductive capacity on Sour Orange, Australian sour orange, and volkameriana, showing higher root and soil infestation rates, with respectively 466.3, 250.5, and 273.3 females/10 g of root, and 1062.2, 1030.7, and 1053.2 females per 100 g of soil, compared to the other rootstocks varieties. These rootstocks allowed highest T. semipenetrans reproduction rates in both rhizospheric soil (> 3) and root (> 0.68), they also showed the highest infestation rate with more than 3 nematodes per cm of root. Moreover, these rootstocks showed significant biochemical alterations including a sharp increase in the activity of antioxidant enzymes, catalase (CAT), peroxidase (PO), polyphenol-oxidase (PPO), and in proline and malondialdehyde (MDA) accumulation compared to the control and other tested rootstocks. In contrast, T. semipenetrans reproduced poorly (with less than 135 females/10 g of root), less infested the roots (less than 0.33 females/cm of root), and induced slight biochemical modifications in Carrizo citrange. Thus, Carrizo citrange endowed with high resistance to T. semipenetrans could serve as a suitable rootstock to control this citrus devastating nematode.