The Portugal captain scored in the 65th minute from the penalty spot -- the 118th goal for his country -- to open the scoring at Doha's Stadium 974. Portugal went on to win 3-2 as goals from Joao Felix and Rafael Leao helped them weather two late efforts from Ghana.
Ronaldo, 37, is the most prolific goal scorer in men's international football and has made a record 18 appearances for Portugal at a World Cup.
"It's a beautiful moment, in my fifth World Cup. We won, we started off on the right foot, a very important victory," Ronaldo said of the milestone. "We know that in these competitions winning the first game is crucial. Another record too, the only player to score in five consecutive World Cups, that for me it is a reason of great pride.
"I am very happy for the team to have given an excellent performance. Difficult, but fair win.
"The important thing was that the team won. The [Manchester United] chapter is closed, and the focus is solely and exclusively on the World Cup. As I said, we wanted to start off on the right foot. We won, we played well, I helped the team. Everything else is not important. The important thing is the national team."
The forward made his Portugal debut in 2003 and scored his first goal 10 months later during a Euro 2004 group stage game against Greece.
His first World Cup goal, in 2006, was from the penalty spot in a 2-0 win over Iran. His next World Cup goal came four years later in South Africa in a 7-0 rout of North Korea. Ronaldo also scored in Portugal's 2-1 win over Ghana in the 2014 World Cup in Brazil, but his side faced disappointment as they were eliminated in the group stage.
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Ronaldo's most successful World Cup campaign was in 2018 in Russia, where he scored four goals, including a hat trick in a 3-3 draw with Spain. The last of those goals came in the 88th minute, a 25-yard free-kick that flew into the top left corner past United teammate David de Gea.
RONALDO MAKES HISTORY
With this goal, he becomes the first men's player to score in five different FIFA World Cup tournaments ??? pic.twitter.com/PxWP4Z5z8o— FOX Soccer (@FOXSoccer) November 24, 2022
Portugal's best performance with Ronaldo was the 2006 World Cup, when they finished fourth.
By scoring in Thursday's Group H game against Ghana, his eighth goal at a World Cup, he is one strike from equalling the country's record in the competition, set by Portugal legend Eusebio. Eusebio helped Portugal reach third place at the 1966 World Cup in London, where he finished as the top scorer with nine goals.
Ronaldo's finest hour in international football came when he captained Portugal to Euro 2016 glory against hosts France with a 1-0 victory. It was Portugal's first major title, and it was followed by UEFA Nations League glory three years later.
Cristiano Ronaldo wrote on Instagram: "Very important win in our World Cup opener but nothing is won! It was just the first step! We remain focused on the pursuit of our objectives. Strength Portugal!"