The role of secondary metabolites (SMs) in Amaranthus plant defense is a poorly studied field. Different cultivars of amaranth have shown varying degrees of susceptibility to insect attack in the field, and previous research has discussed the potential role of these compounds as insect phagodeterrents. In this study, we measured the content of five hydroxybenzoic acids, three hydroxycinnamic acids, and three flavonoids in 30-days-old undamaged plants, over two consecutive years. In addition, we examined the impact of SM content in the leaves of amaranth cultivars on food preference and the rate of plant tissue utilization by the generalist insect Spodoptera frugiperda. In the first year, experiments were conducted using two cultivars: A. cruentus (1) and A. mantegazzianus (1), while the second-year experiments included three cultivars of A. hypochondriacus (a total of five cultivars). Our results showed that, under identical growth conditions and in the absence of stress, flavonoid content emerged as the most consistent trait for distinguishing between cultivars, with rutin being the key variable accounting for the observed variability. In contrast, the contents of hydroxybenzoic and hydroxycinnamic acids exhibited significant variability among cultivars and between years. Additionally, we observed that high concentrations of phenolic acids in plant tissue correlated with lower rates of food utilization by S. frugiperda, without affecting preference indices. The potential defensive capabilities of these SMs for mitigating insect herbivory damage in amaranth crops are discussed in this work.