Lettuce (Lactuca sativa L.) is one of the most important leafy greens worldwide. Nutritional value of its edible leaf depends on different factors including lettuce’s type and growing conditions. The aim of this study was to investigate bioactive compounds accumulation, antioxidant activity and growth behavior of twenty-two lettuce genotypes, cultivated under field and greenhouse conditions. Total phenolic compound, chlorophylls, carotenoids, anthocyanin contents, and antioxidant activities were analyzed by spectrophotometric methods. The data were examined with ANOVA and further explored by principal component analysis. Significant differences between bioactive compounds, antioxidant activity and growth behavior were found among cultivars and morphological types, for both growth conditions. Carotenoid and chlorophylls content was higher in greenhouse conditions for all genotypes. In field production, butterhead and iceberg lettuces showed lowers content of these bioactive compounds. The red-pigmented Falbala cultivar from field production showed the highest level of polyphenols and anthocyanin. Meanwhile, in greenhouse condition, the oak leaf cultivar Grenadine displayed the highest concentration of these phenolic compounds. The iceberg type lettuces showed the lowers percentages of antioxidant activity in both environments. The results point out the impact of growth conditions and the high variability in lettuce bioactive compounds accumulation and antioxidant activity.