The Blues never quite recovered from going two goals down inside the first 20 minutes and despite Yaya Toure and Sergio Aguero bringing City back to level terms, an elusive winner just wouldn’t come.
And there was drama in the dying seconds as Aguero appeared to have a perfectly good goal disallowed a minute from normal time and Mario Balotelli was denied what looked a certain penalty with the last act of the game.
It just wasn’t the Blues’ night.
Mancini went with the front pairing that so often delivers in Aguero and Carlos Tevez while Javi Garcia was drafted in to form a holding midfield partnership with Gareth Barry.
With Yaya unleashed so to speak, there was no need for the three strikers that began against West Ham – a game that the City boss claimed his team had missed four or five incredible chances.
City knew it was win or bust against the Eredivisie champions and began like a team on a mission with slick passing and excellent movement from the word go and had Pablo Zabaleta tucked away a chance on seven minutes, the Blues could have had the goal their early play deserved.
Instead, they found themselves behind when Ajax scored with virtually their first attack as Siem de Jong finished emphatically from close range on nine minutes. It was cruel but yet again underlined how mistakes in the competition are so frequently punished.
A drama then became a crisis with a second goal for Ajax seven minutes later – one that will give City’s defenders nightmares for weeks to come as de Jong ran unchallenged to glance a Christian Eriksen corner powerfully past Joe Hart.
Two goals down and seemingly heading out of the Champions League at the earliest possible opportunity – yet the Blues, bizarrely, were playing well! Two moments of defensive madness had given the game a surreal score-line, but City continued to plug away.
Nobody could question the effort Mancini’s side were showing and on 22 minutes – at last – a lifeline as Nasri’s lofted cross found Yaya Toure at the far post and the Ivory Coast star who controlled the ball on his chest before spinning to volley home a superb shot past Kenneth Vermeer.
Suddenly, there was hope again.
Mario Balotelli replaced Garcia at the break and Edin Dzeko came on for the hard-working Tevez as City went for broke, looking for the two goals that would give them victory.
Ajax, however, defended stubbornly and still carried a real threat on the break, particularly as the Blues started to tire and gaps appeared at the back and de Jong was denied a hat-trick from a free-kick that Hart did well to keep out.
Just when it seemed City had run out of ideas, a long ball up to Balotelli saw the Italian flick the ball into the path of Aguero who drilled a low ball past Vermeer to make it 2-2 and set up a grandstand finish.
Balotelli, having a real impact from the bench, saw a powerful header clawed away by Vermeer and TV replays suggested Aguero’s 89th-minute goal should have stood – but sub Aleksandar Kolarov, who crossed the ball in - was flagged offside – and how crucial that decision proved to be.
And there was futher controversy when the referee denied Balotelli a last-gasp penalty as he was pulled back in the box causing the City players to react furiously at the Danish official who instead blew for full-time.
The home crowd showed their appreciation at the final whistle, but the Blues are now reliant on a series results of going their way as well - plus the small matter of having to beat Real Madrid and Borussia Dortmund!
Unlikely, but not impossible...
