The 41-year-old had gone into the game under intense scrutiny after failing to score in the 1-1 draw with DR Congo last week, with some calling for Roberto Martinez to drop him entirely. He answered within six minutes, turning home a near-post finish to open the scoring and become Portugal's all-time leading World Cup scorer with his 10th tournament goal — breaking the record previously held by Eusébio.
A second before half-time, latching onto a Bruno Fernandes through ball to roll coolly past goalkeeper Abduvohid Nematov, took Portugal into the interval 3-0 ahead, with Nuno Mendes having added the second via a clever free-kick routine.
Ronaldo chased a hat-trick throughout the second half but was denied by Nematov on several occasions. A fourth came from the Uzbek goalkeeper's own account, the ball deflecting in off him from a João Félix back-flick, before substitute Rafael Leão lashed home a fifth in the 87th minute.
The victory moves Portugal top of Group K on four points, one ahead of Colombia. Uzbekistan, playing at their first World Cup, are effectively eliminated. Portugal face Colombia on Sunday to determine who tops the group.
Facing reporters after the final whistle, Ronaldo stared into a television camera and shouted "I'm back! I'm back!" — a message directed at those who had questioned his place in the team. When asked about the statement, he said it was "only so they [his critics] don't forget — 23 years doing so like this."
"I'm very happy but the most important thing is the work the team did and the confidence it gives us," Ronaldo added.
"Obviously personal records are always nice but my goal is always to help the team achieve its objectives.
"We had to get through many obstacles during the week but the team worked very well, we improved a lot.
"It's been a difficult week, a dark week without kicking a ball, but we dealt with it as we always do because we believe in our work. It was difficult, but we're back."
Manager Roberto Martinez said the squad had grown through the adversity of the previous week.
"It was a difficult week because we hadn't achieved the result we were aiming for and we had a difficult situation with criticism, noise — which was actually unfair," he said.
"We were raging, we were sick, but we grew as a team, overcame emotions and have been able to give our very best. Cristiano Ronaldo was a perfect captain, very much focused and made use of his experience because it is not the first time he deals with this situation.
"Our captain is an icon, he is playing in his sixth World Cup. He is a role model that plays for the Portuguese national team, that works hard every day, that tries to improve every training session and with a great attitude on the pitch and also in the dressing room."
Uzbekistan head coach Fabio Cannavaro, a World Cup winner with Italy in 2006, was generous in his assessment of Ronaldo's enduring quality.
"You come to the World Cup and show that when you are 41 you are still hungry and can do a lot," said Cannavaro. "You don't forget how to play football. He is part of the history of the World Cup.
"Football is not only in Europe, it's open to the whole world. There are no horizons or borders anymore. Cristiano is still one of the strongest players in the history of football. If you give him one centimetre in the box you are dead."
At 41 years and 138 days, Ronaldo is now the second-oldest scorer in World Cup history behind Roger Milla, who netted for Cameroon at the age of 42 in 1994. His brace brought his international tally to 145 goals, a record he holds by 23 over Lionel Messi.