Mastantuono struck twice in the space of 97 seconds either side of the half-hour mark to help Fiorentina come from behind, before completing his treble six minutes from time as the Viola secured their first points of the Serie A season.
At 19 years and 28 days old, the Argentine became the youngest player in the club's history to score a Serie A hat-trick, surpassing a record previously held by club legend Gabriel Batistuta, and the ninth-youngest to do so in the competition's history.
"For me it's an honour to become part of the history of such a prestigious club," Mastantuono told DAZN. "It was important to get the result, we played a great match today. Happy for the win as well as the goals."
The performance also eclipsed Lionel Messi's own youngest hat-trick record in Europe's top five leagues, with Mastantuono 231 days younger than Messi was when he scored his first Barcelona hat-trick against Real Madrid in 2007. The goals were also his first in Serie A, having gone without scoring in his first three appearances since arriving on a season-long loan from Real Madrid last month.
Asked whether he wanted to hand his man-of-the-match award to teammate Nicolo Fagioli, who set up Mateo Pellegrino's goal in the win, Mastantuono was quick to share the credit.
"He had a great game, like the whole team. Very happy for the win," he said.
The result, Paolo Vanoli's first match back in charge after being recalled to replace the sacked Fabio Grosso, lifted Fiorentina off the bottom of the table and up to 15th, while Venezia FC dropped into last place having also failed to register a win in four matches.
Mastantuono, who made his senior debut for River Plate at 16 before moving to Real Madrid last year, is regarded as one of the most promising young talents in world football, and became Argentina's youngest ever senior international when he made his debut for the national team in June 2025.
His hat-trick matched the number of goals he managed in 35 appearances for Real Madrid last season.