The 41-year-old Portugal skipper, under pressure to find the net after a barren run at major international tournaments, pounced from close range after just six minutes to create a piece of World Cup history.
It is testament to Ronaldo's longevity, the former Manchester United, Real Madrid and Juventus superstar having scored his first World Cup goal in 2006, against Iran.
Ronaldo faced flak after being largely anonymous in a disappointing 1-1 draw with the Democratic Republic of Congo that started Portugal's World Cup title bid in North America.
In his previous 10 games at major competitions coming into the Uzbekistan match, he had zero goals and one assist.
His travails in front of goal were in glaring contrast to the likes of Lionel Messi, Kylian Mbappe, Erling Haaland and Harry Kane.
Ronaldo, widely recognised as one of the best players in football history, made his international debut in 2003.
Now with Al Nassr in Saudi Arabia, he scored 28 goals in 30 league games this season.
Ronaldo nearly struck after just three minutes in Houston, narrowly failing to make contact at the far post after a cross by Nuno Mendes.
Ronaldo slapped the turf, but the frustration was to be only temporary.