Pennetta became, at 33, the oldest first-time Grand Slam women’s champion in the Open era with the 93-minute triumph.
“It’s a dream come true,” Pennetta said.
But only moments after accepting the trophy, she said she had decided to retire after her ultimate victory.
“This is the way I would like to say goodbye to tennis,” Pennetta said. “I’m really happy.”
The only other Italian woman to win a major singles title was Francesca Schiavone, who captured the 2010 French Open and set the former oldest first-timer age mark at 29.
“I’m really happy right now,” said Pennetta, a 150-1 longshot to win the title when the Flushing Meadows fortnight began.
“Before this tournament I never think to be so far. I never think to be a champion. When things come like this it’s a big surprise to me.”
Italian prime minister Matteo Renzi was among 23,771 in Arthur Ashe Stadium watching the first all-Italian women’s Grand Slam final of the Open Era.
Pennetta took the top prize of $3.3 million (2.9 million euros), while runner-up Vinci received $1.6 million.
Pennetta previously had won only $712,401 this year while Vinci’s 2015 prize money before Sunday was $422,158.
The breakthrough win came in Pennetta’s 49th Grand Slam appearance, the most needed for any women’s major champion, two more than France’s Marion Bartoli when she won at Wimbledon in 2013.
“Always when I was younger I was thinking to be number one,” Pennetta said. “I was also thinking to win Rome but I think Grand Slam may be a little better.”
Pennetta, ranked 26th, and Vinci, ranked 43rd, each played in her first Grand Slam final after pulling a semi-final shocker.
Vinci shattered the hopes of Serena Williams to achieve the first calendar Slam since 1988 with a semi-final win over the top-ranked defending champion whilePennetta dispatched Romania’s second-ranked Simona Halep.
“It was tough,” Vinci said of returning after the emotional drain of ousting Williams.
“I passed the 24 hours with a lot of things on my mind. I was really tired especially in the first set, but I was in the US Open final so I was really happy.”
Friends since childhood in southern Italy, Vinci, 32, and Pennetta had the oldest combined ages of any Open Era Grand Slam final duo, beating the former mark of just under 64 years from when Virginia Wade beat Betty Stove in the 1977 Wimbledon final.
“It’s tough to play against one player you know from a long time,” Vinci said. “Was tough today but I tried to do my best. Flavia played unbelievable today. Great match.”
Pennetta, who took a 6-4 lead in the career rivalry, leaped to a career-best eighth in the rankings with her 11th career title, the first since last year at Indian Wells.
The first US Open women’s championship match between Grand Slam finalist debutantes saw Pennetta force seven break points against Vinci before breaking through for a 3-2 edge in the first set.
Vinci hit a backhand crosscourt winner to earn her first break point in the eighth game and Pennetta netted a backhand to pull Vinci even at 4-4 on the way to a tie-break.
Pennetta won five of the last seven points in the decider, the last on a service winner to claim the opening set after an hour.
Pennetta broke Vinci for a 2-0 lead and moved ahead 4-0 when Vinci netted a backhand to surrender another break.
Vinci broke back in the fifth game, a Pennetta drop shot leading to a Vinci overhead smash, and held but Pennetta regained momentum with a lob winner to hold and grab a 5-2 edge, then broke for the win.