The top seed beat second in just under an hour-and-a-half at Estadio Nacional to become only the third player to successfully defend an ATP 250 trophy on clay.
It was also Del Potro’s 11th career title as he continues his rise up the rankings after injuries saw him drop to world number 485 just over a year ago.
"I felt I played well really well today," said del Potro, 23. "I felt it was my best match of the week, so I am very glad for that to get another title in Estoril.
"I play really aggressive all the time and I felt really confident on my forehand. I grew in confidence every game. It is important for me. I played my best to beat Gasquet.
"I am getting closer and closer to my best form. I have worked really hard at home and now I have another important tournament next week to improve further. If I play as well as I did today over the coming days, I will be happy."
The Argentine, who provisionally rises to world number nine after the win, made relatively light work of the Frenchman, holding serve throughout and breaking his opponent three times.
Indeed, Del Potro opened both sets with breaks, winning the first with a hold to love and cruising to take the second in just over half an hour.