Responses of Atriplex portulacoides upon 40-day-long exposure to salinity (0–1,000 mM NaCl) were investigated. Mother plants originated from a sabkha located in a semi-arid region of Tunisia. The plant relative growth rate and leaf expansion increased significantly at 200 mM NaCl but decreased at higher salinities. Interestingly, the plants survived salinity as high as 1,000 mM NaCl without displaying salt-induced toxicity symptoms. Despite significant increase in leaf Na+ and Cl− concentrations upon salt treatment, no significant effect on leaf relative water content was registered. Chlorophyll contents and the gas exchange parameters showed a significant stimulation at the optimal salinity (200 mM NaCl) followed by a decline at higher salinities. Extreme salinity hardly impacted the maximal efficiency of photosystem II photochemistry (Fv/Fm), but a marked decrease in the relative quantum yield of photosystem II (ФPSII) was observed, along with a significant increase in non-photochemical quenching (NPQ). Leaf malondialdehyde and carotenoid contents were generally unaffected following salt exposure, whereas those of anthocyanins, polyphenols, and proline increased significantly, being maximal at 1,000 mM NaCl. Leaf superoxide dismutase (EC 1.15.1.1), ascorbate peroxidase (EC 1.11.1.11), and glutathione reductase (EC 1.6.4.2) activities were significantly stimulated by salinity, whereas catalase (EC 1.11.1.6) activity was maximal in the 0–400 mM NaCl range. As a whole, protecting the photosynthetic machinery from salt-induced photodamage together with the sustained antioxidant activity may account for the performance of A. portulacoides under high salinity.