The win, albeit against a largely second-string Portugal who had already made it into the next round, also represented the greatest result for Georgia since the country gained independence from the Soviet Union in 1991.
Coming from a disappointing fourth in their Euro qualifying group, Georgia had to take a circuitous route to Germany, first by winning their group in the less glamorous UEFA Nations League tournament then by defeating Greece in a playoff.
But there was nothing undeserved the way coach Willy Sagnol, the former Bayern Munich and France defender, and his side claimed a third-place finish in the tournament's Group F and set up a last-16 meeting with three-time Euro winners Spain.
When those two sides met in September during the qualifying stage for the tournament in Germany, Spain thrashed Georgia 7-1 in Tbilisi.
"When you are the small team of the competition ... you know you have nothing to lose...You have no weight on your shoulders," Sagnol told reporters. "Today I don't have a lot of words. I feel very proud to be their manager."
Georgia's win also means that England will line up against Slovakia, Romania will take on Netherlands and Portugal will face Slovenia in the round of 16. Hungary, who had been in contention for a spot in the next round, were edged out.
In the other Group F match on Wednesday, Turkey booked their place in the round of 16 with a 2-1 win over 10-man Czechia, who now head home.
Georgia, the tournament debutants, took the lead in the second minute when Kvaratskhelia, the Napoli winger, raced away after a careless pass by António Silva and powered a low shot past Diogo Costa in Portugal's goal.
"We can fight against everyone," Kvaratskhelia told reporters after. "I'm so proud."
Ronaldo -- one of only three starters for Portugal who also played in their 3-0 win over Turkey on Saturday -- stretched and strained for every ball as he sought to become the oldest goal scorer at a Euro tournament at the age of 39.
But Georgia defended as if their lives depended upon it and sought to catch Portugal on the break. In the 53rd minute, Silva compounded his earlier error by committing a foul in the box that was given as a penalty after a VAR check.
Information from , The and ESPN Stats & Information contributed to this report.