Juventus splashed out 100 million euros ($117 million) on the five-time Champions League winner last summer and the Portuguese star headed in his 126th Champions League goal to put the home team in front on Tuesday.
But a devastating young Ajax team, spearheaded by 19-year-old defender Matthijs De Ligt, ran riot in the second half in Turin to seal a famous 3-2 aggregate victory.
"Apocalypse," read the headline in daily Corriere dello sport, as Juventus shares plunged 15 percent on Wednesday on the Milan stock exchange.
"Not even a huge investment like Ronaldo was enough to win a title that Juve have been searching for since 1996," the sports daily added.
Juventus have lost five times in the final since 1996 when they won their last title, at the expense of Ajax.
Ronaldo was bought to change that and was handed an annual salary of 31 million euros. He has won the title five times and scored a 97th-minute penalty for Real Madrid against Juventus last season in the quarter-finals.
Coach Massimiliano Allegri said he had no regrets, blaming injuries for the team's failure to progress.
"Football isn't maths," said Allegri.
"Ronaldo gave us a lot during the season. We signed him to increase our chances of winning the Champions League, but in football one plus one does not always make two, it can also be either six or zero.
"I have always said that you have to arrive at the right time in the best condition, when you reach the quarter-final, you need every player.
"We've been in a bit of an emergency situation for a while and that can only be sustained for so long.
"We were missing four or five players."
- End of Ronaldo era -
For the first time since 2010, Ronaldo will not be in the Champions League semi-finals.
And he held his head in his hands in despair as he slumped to the pitch at the Allianz Stadium.
He had single-handedly lifted Juventus into the quarter-final with a stunning hat-trick in the second leg against Atletico Madrid.
But he was unable to lift his team to a Champions League title he had won in the three previous seasons and in 2014 with Real Madrid, as well as with Manchester United 11 years ago.
He holds the record for goals scored -- which includes 65 goals in the knockout rounds, another record.
Rival Lionel Messi is second on 110 goals after his double for Barcelona against Manchester United on Tuesday.
"Ajax deserved to qualify and you saw that on the pitch," said Juventus president Andrea Agnelli, who said Allegri would be continuing as coach.
Ironically Agnelli -- who is also president of the European Clubs Association (ECA) -- is the driving force behind moves to change the Champions League and make it even harder for teams from smaller countries, like Ajax, to qualify.
Agnelli, 43, stressed that the team was growing.
"For our part, we are aware of having been in the Champions League quarter-finals for five or six years and are proud to continue this path," said Agnelli.
Although Juventus are on course to seal an eighth consecutive Serie A title next weekend, they are out of the Coppa Italia, which they had won the four previous seasons.
"I'm looking at the big picture," Agnelli said.
"We played a great return match against Atletico, and just a few years ago Juventus were 43rd in the European rankings, today we are fifth and this is the sign of the progress that continues.
"A few years ago, the Champions League was a dream, this summer it was a goal and it will be next year too."
Ronaldo was a heavy investment with the club announcing expected losses for this season, having gone 19.2 million euros into the red for the 2017/2018 campaign.
Ajax, meanwhile, reached their first semi-final since 1997.
"You could see that Juve were a little scared of us and so were Real Madrid," said coach Erik ten Hag. "It is very difficult to play against our style of football, as we have very technically-gifted players."