Novel nano-based fertilizers, pesticides, sensors, and nutrient delivery systems for agricultural applications have been widely reported. However, several key questions remain regarding nanoparticle (NP)–plant interactions, such as the impact of interactions of co-existing NPs on their accumulation in plants, especially in plants grown in soil systems. In this study, soil-grown lettuce was exposed to different concentrations of silver nanoparticles (AgNPs) alone (0–200 mg/kg) or in combination with 100 mg/kg cerium oxide nanoparticles (CeO2NPs) in a greenhouse study. As expected, the concentrations of AgNPs and CeO2NPs in plant tissues were markedly increased in plant tissues grown in NP-treated soil. Surprisingly, the size of AgNPs in roots was much smaller than those in shoots and in freshly prepared suspensions, suggesting that smaller AgNPs were preferably taken up by plant roots and then aggregated into large NPs in lettuce shoots. The noticeably smaller AgNPs might stem from the dissolution of AgNPs in the rhizosphere or the formation of transformed Ag-containing NPs from dissolved Ag+. CeO2NPs significantly modified the uptake and in planta distribution of AgNPs in lettuce. For example, the co-presence of CeO2NPs in soil notably increased the concentration of AgNPs in lettuce shoots but significantly reduced their concentration in roots, compared with 100 mg/kg AgNPs treatment alone. The total concentrations of zinc (Zn) and copper (Cu) in plant tissues were determined as representative micronutrients and compared with those of the control; 100 mg/kg AgNPs diminished the Zn and Cu concentrations in lettuce, but there was no significant effect when AgNPs and CeO2NPs were co-available in the soil. These results shed new light on plant–NP interactions in soil ecosystems exposed to multiple NPs at the same time.