Small succulent halophytic shrubs of the genera Salicornia and Sarcocornia (Salicornioideae, Amaranthaceae) are commonly named sea asparagus and consumed worldwide as green salad in gourmet food, as conserves, and beverages. Their shoots are rich in bioactive compounds and plants show high yields in a wide range of salinities, but little is known about how salt cultivation conditions affect their chemical composition. Two genotypes (BTH1 and BTH2) of the Brazilian sea asparagus Salicornia neei Lag. were evaluated for salt tolerance and changes in shoot concentrations of organic metabolites and antioxidant activity under different salt exposure in both greenhouse and field conditions. All greenhouse plants received full strength modified Hoagland solution in deionized water with a basic electrical conductivity (EC) of 1.7 dS m⁻¹, and with NaCl concentrations (in mM) of ~0.1 (control), 34, 86, 171, 513, and 769. After fifty days of cultivation, both S. neei genotypes showed high salt tolerance and grew better under low salinities (34–86 mM NaCl) than under control salinity. Shoots of BTH1 genotype appeared to be undergoing lignification and used their high carotenoid content to dissipate the oxidative power, and the zeaxanthin content and de-epoxidation state of xanthophylls (DES) were positively affected by salinity. Under increasing salinity, BTH2 genotype had higher relative content of chlorophyll b, which may have lowered the plant photo-oxidation rate, and increased shoot concentration of the flavonoid quercetin (up to 11.6 μg g⁻¹ dw at 769 mM NaCl), leading to higher antioxidant capacity. In the field experiment, after 154 days of irrigation with saline (213 mM NaCl) shrimp farm effluent, BTH2 plants grew taller, produced more metabolites (e.g., total phenolics, total free flavonoids, quercetin, and protocatechuic acid) and had a greater antioxidant capacity of shoots than that of BTH1 plants and that of traditional crops irrigated with fresh water. Yield and bioactive compound composition of S. neei genotypes’ shoots can be enhanced by cultivation under moderate saline conditions.