Reports on the presence and toxicity of Pb2+ in various chemical industrial effluents energized researchers to investigate several feasible, efficient, precise, and sensitive techniques for determining and removing Pb2+ from aqueous systems. The current work proposes the adsorption of Pb2+ onto the stem of parthenium as a continuation of a series of investigations. In order to find the ideal circumstances for the most effective removal of lead, optimization of Pb2+ sorption potential-affecting factors, such as pH, contact duration, temperature, adsorbent dosage, and concentration of Pb2+ as sorbate, were investigated. The response surface approach was used to assess experiments that were carried out using a rotatable Box-Behnken design (BBD) (RSM). The influence of three independent variables—the pH of the precursor solution (4–5), the initial lead content (15–25 mg/l), and the dose of biomass (20–40 g/l)—were assessed in response to the biosorption process. The optimum pH, lead ion concentration, and biomass dosage for lead biosorption were ascertained to be 5 pH, 20 mg/L, and 30 g/L, respectively. The Parthenium stem powder can reduce the concentration of lead in an aqueous solution by up to 72.74% for 20 mg/l at pH=5 and 260 °C. It has been shown that 1.5 g/100 ml of parthenium stem powder and a 50-minute equilibrium duration are the most effective parameters. The amount of lead absorbed from the aqueous solution increases with an increase in the adsorbent's dosage. Freundlich and Langmuir models in both linear and nonlinear variants were used to comprehend the nature of the adsorption process. By analysing the kinetics and thermodynamics of the process, the feasibility and viability of the sorption process were assessed. The adsorption process was quite rapid, according to the kinetic analyses, and equilibrium was attained after 50 min of contact time. The spontaneous nature of the adsorption process was revealed by the negative values of free energy change. Studies on thermodynamics showed that reactions were exothermic, although research on kinetics revealed that reactions is indeed pseudo-second order.