Andre Silva scored the only goal as European champions Portugal -- without superstar Cristiano Ronaldo -- got their Nations League campaign off the mark with a 1-0 win over Italy in Lisbon on Monday.
Ronaldo, 33, had been left out of the squad at his own request to focus on his new Italian club Juventus.
But the Euro 2016 winners showed no sign of missing their star striker, dominating the Italians to secure their first three points in a Group 3 that also includes Poland.
Italy coach Roberto Mancini suffered his first competitive setback after being held by Poland 1-1 in their opener on Friday in Bologna, with the Azzurri on one point after two games.
"We made too many mistakes, but the lads gave everything," said Mancini.
"We need to find a solution to scoring goals because you don't win games without scoring. That's our main problem right now.
"Portugal have won the first, so they're the favourite, but I think it's still wide open, you never know in football."
Silva scored three minutes into the second half with AC Milan's on-loan Sevilla striker collecting a Bruma cross to beat his former Milan teammate Gianluigi Donnarumma in the Italy goal.
"I have some friends in the Italian national team, but there are no friends on the pitch," said Silva.
"Overall we were the better team on the night and deserved the win."
Italy had been fortunate to keep their goal clear in the first half, largely thanks to Donnarumma, as Portugal dictated play in the Estadio Da Luz.
Bernardo Silva's effort was cleared off the line by Alessio Romagnoli with a Bruma shot deflected onto the bar.
Italy fought back with Ciro Immobile and Simone Zaza threatening just before the break.
Mancini had rang the changes with an experimental side with seven new players starting -- midfielder Jorginho and Donnarumma the only pair to be retained from the draw with Poland.
- 'Italy take risks' -
In the same 4-3-3 lineup, Lazio striker Immobile came in for Mario Balotelli, who was heavily-criticised for his performance against Poland before coming off with a muscle problem.
SPAL's Manuel Lazzari made his international debut on the right of defense.
Federico Chiesa and Andre Silva both missed chances early, while a Zaza back-heel flick for Immobile was cleared in the box.
William Carvalho fired just wide from distance and Jorginho's volley was cleared.
Portugal grabbed the winner soon after the restart through Silva with Bernardo Silva coming close to a second only for Donnarumma to clear.
Italy struggled to create chances, apart from a Zaza header that went wide 12 minutes from time, as Portugal claimed their ninth straight home win.
The four-time world champions now risk being relegated from their Nations League group after also failing to qualify for the World Cup.
But Mancini defended his experimental side.
"We don't like losing, but it's also true that we have to take risks and get experience in these games, otherwise it's hard to move forward quickly," said the former Manchester City and Inter Milan coach.
"We must help the youth grow, as we don't have alternatives.
"We would like to finish first in the group, you never know in football. We will see what happens, our starting goal is to qualify for the Europeans."
In the three-team group Portugal play in Poland on October 11, with Italy again facing the Poles on October 15.
And Portugal coach Fernando Santos ruled out talk of them now being the favourites.
"Do we have a foot in the final? We need both feet in there, because standing on one foot you risk falling over."