Heavy metals in soils pose a potential threat to the environment and can cause significant damage to human and animal health. This study aimed to assess heavy metal concentrations, photosynthate levels, biochemical characteristics, and anatomical responses in Telfairia occidentalis and Amaranthus hybridus collected within Akure metropolis, Ondo State, Nigeria. Fresh vegetable samples were randomly collected from four fertilized farmlands (denoted as A, B, C, and D) within the Akure metropolis. Heavy metal concentrations in the vegetable samples were determined using an Atomic Absorption Spectrophotometer (AAS). The pigment content (Chlorophyll a and b) of the vegetables was measured, while the activities of Catalase (CAT), Superoxide Dismutase (SOD), and reduced glutathione (GSH) were estimated. Stomatal architecture and epithelial cell structure were also analyzed. Results indicated that CAT (7.45 ± 0.36 U/mg protein) and SOD (6.21 ± 0.28 U/mg protein) activities, as well as GSH content (4.63 ± 0.12 µmol/g tissue), were highest in vegetables collected from farm A, showing statistically significant differences compared to other farms (p < 0.05). The concentrations of heavy metals in the leaves of vegetables collected from all farms were below the standard limits recommended by WHO/FAO, with the exception of Lead (Pb), which was significantly higher than the permissible limit in farm B (2.14 ± 0.09 mg/kg; p < 0.05). Chlorophyll content was significantly reduced in both vegetables compared to the control (chlorophyll a: 2.56 ± 0.21 mg/g tissue in T. occidentalis and 2.03 ± 0.19 mg/g tissue in A. hybridus; p < 0.05). This reduction in chlorophyll content correlated with the elevated levels of Pb in farm B (r = -0.87, p < 0.05). The stomatal architecture analysis revealed significant alterations in stomatal density and pore size in both vegetables from contaminated farms. These findings suggest the need for biomonitoring programs to control heavy metal accumulation in Nigerian farmlands, as elevated levels of Pb can disrupt the physiological and biochemical processes of vegetables, posing potential health risks to consumers.