The top seed and hometown hero needed just 97 minutes to overcome second seed Darderi at the clay-court ATP 250 event, securing his fourth career crown and first on Argentine soil in front of friends and family.
"Probably the best moment of my career so far," Cerundolo said after the victory. "I really wanted to win here in my hometown, in my country, with my friends and family and all the people here in Argentina. This feeling is amazing."
The 27-year-old Cerundolo, who had lost the finals in 2021 and 2023, completed the championship without dropping a set.
The world number 19 saved six of seven break points, including all five in the opening set, to become the seventh home champion at the tournament since it began in 2001.
"I really fought throughout these past years and tried to win. I couldn't do it, and today I played one of the best matches probably of my career," he added.