Portugal did not need Ronaldo — who skipped international duty to recharge after a busy summer — to beat Italy 1-0 in Europe's newest soccer competition.
Elsewhere, Turkey mounted a remarkable comeback from two goals down against Sweden, while Kosovo made history with its first competitive win since being admitted to UEFA in 2016.
The European champions easily outplayed Italy, which had opened its Nations League campaign with a disappointing 1-1 home draw against Poland in its first competitive match under coach Roberto Mancini.
"We must be more effective in attack," Mancini said. "We must find solutions and be able to score goals."
Andre Silva scored on a counterattack early in the second half to give Portugal the Group 3 win in the top-tier League A. The hosts had several chances to extend their lead at the Stadium of Light in Lisbon, while Italy created little and relied mostly on set pieces.
"It was a fair result, we played better throughout the match," said Portugal coach Fernando Santos, who led his team to its ninth straight home win. "Only in the final 10 minutes we slowed our pace a bit and that allowed Italy to grow."
The Nations League gives UEFA's 55 member countries competitive games and eliminates friendlies. The winners of the League A groups — featuring the highest-ranked countries — go into a final-four competition in June.
Santos did not call up Ronaldo after talking to the player and saying he needed more rest following the World Cup and his transfer from Real Madrid to Juventus. Ronaldo also didn't play in the team's 1-1 draw in a friendly against Croatia last week.
Social media photos showed Ronaldo and his family enjoying time off in Monaco in recent days.
It was Italy's second competitive match since last year's World Cup playoff loss to Sweden.
"There is work to do," Italy midfielder Giacomo Bonaventura said. "We wanted to threaten them but we didn't manage it and we're really disappointed."
HISTORIC KOSOVO
Two goals five minutes apart early in the second half gave Kosovo a historic 2-0 win over the Faroe Islands in Group 3 of the fourth-tier League D.
Kosovo, the Balkan republic which was accepted by UEFA and FIFA two years ago, had opened with a 0-0 draw at Azerbaijan.
TURKEY BEATS SWEDEN
Turkey bounced back from an opening loss to Russia by coming from two goals down to defeat Sweden 3-2 thanks to two late goals by Emre Akbaba.
Akbaba scored in the 88th minute and two minutes into stoppage time to give Turkey the League B victory.
Sweden, making its Nations League debut following its surprising quarterfinal appearance at the World Cup, had taken a 2-0 lead by the 49th minute at Friends Arena in Stockholm.
It was Turkey's first away win in seven matches.
LOWER LEAGUES
In the third-tier League C, Scotland ended its run of three straight losses with a 2-0 win over Albania in Group 1.
In Group 4, Serbia and Romania drew 2-2, while Montenegro defeated Lithuania 2-0.
In League D, Andorra and Kazakhstan drew 1-1 in Group 1, while Malta drew with Azerbaijan 1-1 in Group 3.
The Nations League guarantees at least one of Europe's low-ranked League D teams will qualify for Euro 2020 through a playoffs.