Layered double hydroxides (LDH) have exhibited promising applications as electrocatalysts in oxygen evolution reactions (OER). In this work, trimetallic LDHs (CoNiFe-LDH) were designed and grown on graphene (G) through a one-step hydrothermal approach to obtain a structure that promotes efficient charge transfer. A 2- level full-factorial design was utilized to evaluate the effects of varying the concentrations of Co (1.5, 3, and 4.5 mmol) and graphene (10, 30, and 50 mg) on the OER activity. The potential needed to deliver 10 mA cm−2 was chosen as the response parameter. The independent and dependent parameters were fitted to a linear model equation through ANOVA analysis. The computed p-values were below 0.05 signifying the statistical significance of the concentrations of cobalt and graphene and their interaction, suggesting a correlation with the OER activity. The OER experiments were conducted in triplicate using the Co[3]Ni[3]Fe[3]-LDH/G[30] (central point) to estimate variability (0.58%). Comparative analysis showed that Co[1.5]Ni[3]Fe[3]-LDH/G[10] achieved the lowest onset potential (1.54 V), potential at 10 mA cm−2 (1.58 V), and Tafel slope (58.4 mV dec−1 ), indicating that a low concentration of cobalt and graphene make an efficient electrocatalyst for OER. Furthermore, the optimized composite demonstrated favorable electronic properties, with a charge transfer resistance (RCT) of 188.1 Ω, and exhibited good stability, maintaining its catalytic activity with no significant loss over a 24-h period.