Selenium (Se) is necessary for plants in trace amounts, whereas lead (Pb) is a hazardous that hinders their growth. To fill a gap in the existing literature, we intentionally subjected plants to 50 mM Pb concentration to investigate their immediate molecular, physiological, and biochemical responses, as well as the potential of Se seed priming to mitigate the anticipated adverse response. Vicia faba seeds were primed by soaking in a 100 μM Se solution for 12 h or in water for control. The two-week-old plants experienced a transient stress for three successive days by Pb foliar spray (50 mM). The molecular, physiological, and biochemical responses of the four-weeks-old plants were examined. The short-term exposure to 50 mM Pb via foliar spray resulted in minimal visible phytotoxic effects; however, decreased growth parameters were observed, indicating that while acute toxicity is not apparent, physiological stress exists. This was evidenced by a marked reduction in photosynthetic pigment content and capacity, alongside an increase in stress markers: malondialdehyde (48.56%), H2O2 (68.11%), electrolyte leakage (22.36%), and lipoxygenase (35.43%). Se priming significantly reduced all these stress markers. Under Pb stress, Se priming resulted in significant increases in shoot length (20.5%), fresh weight (31.3%), and leaf area (27.6%), along with enhancements in gas exchange parameters, including photosynthetic rate (68.2%) and chlorophyll a and b contents (17.5%). Furthermore, it significantly enhanced the levels of antioxidant compounds by increasing total phenolics (16.6%), proline (28.3%), glycine betaine (10.9%), total thiol (13.6%), and total antioxidant capacity (33.3%) compared to Pb stress alone. Significant upregulation of stress-signaling genes was observed in Se-primed plants exposed to Pb stress, specifically in the ribulose-bisphosphate carboxylase oxygenase, P-type plasma membrane H+-ATPase, and calcium-dependent protein kinase. Additionally, Se seed priming reduced Pb translocation by lowering the translocation factor to 0.57 from 0.7 in non-Se-primed Pb-stressed plants. This experimental approach illuminates the rapid physiological defense mechanisms, transcriptional response of certain stress and signaling genes, and resilience to Pb stress via Se seed priming to support plant development in Pb-contaminated environments.