The former world number three won 6-4, 6-7(3), 6-3 in the clay-court tournament to lift the 13th trophy of his career and first since Dubai in March 2025.
The 27-year-old has dropped to 85th in the world from his career-high ranking of three in 2021 and reached two Grand Slam finals in the French Open that year and the Australian Open in 2023.
Tsitsipas also won the ATP Masters in London in 2019 and the Monte Carlo Masters three times in 2021, 2022 and 2024.
Collignon, a 24-year-old ranked 42nd in the world, was playing his first ATP final, having saved a match point to defeat Argentine Juan Manuel Cerundolo in the semi-finals.
"We both really want it," Tsitsipas said after coming through three sets in the semi-finals.
"We've come to the end, the two of us, so I feel like no one wants to go out there and not give it their all. It’s one last breath. I want to get out there and take the court by storm.”