Global pollution caused by micro/nanoplastics (M/NPs) is threatening agro-ecosystems, compromising food security and human health. Also, the increasing use of graphene-family nanomaterials (GFNs) in agricultural products has led to their widespread presence in agricultural systems. However, there is a large gap in the literature on the combined effects of MNPs and GFNs on agricultural plants. This study was conducted to explore the individual and combined impacts of polystyrene microplastics (PSMPs, 1 μm) or nanoplastics (PSNPs, 50–100 nm), along with agriculturally relevant graphene oxide (GO), on the seed germination and seedling growth of lettuce (Lactuca sativa). The results showed that the combined effects of mixtures of PSMPs/PSNPs and GO exhibited both synergism and antagonism, depending on different toxicity indicators. The cellular mechanism underlying the combined effects on the roots and shoots of seedlings involved oxidative stress. Three SOD family genes, namely, Cu/Zn-SOD, Fe-SOD, and Mn-SOD, played an important role in regulating the antioxidant defense system of seedlings. The extent of their contribution to this regulation was associated with both the distinct plastic particle sizes and the specific tissue locations within the seedlings.