Former City star Edin Dzeko scored the opener six minutes in and Daniele De Rossi netted a penalty with just over half an hour to go. Barca were stunned, many people's favourites for the competition were now staring down the barrel of a quarter-final exit for the second year running.
Ter Stegen parried a Stephan El Shaarawy effort away from the goal-line shortly after he arrived from the bench, but the decisive goal would soon arrive as Manolas nodded beyond the rooted goalkeeper from Cengiz Under's corner.
Barcelona was 90 minutes away from a return to the Champions League semifinals, but if failed to finish off Roma and is shockingly on the outside looking in for Europe's final four. They played with the same spirit that they did in Catalunya.
"Although we have had very good performances in Serie A, we are only now reaping the rewards - the just rewards - for the hard work we have done".
That famous night in Istanbul.
Eusebio Di Francesco implored his Roma players to pull off the "unthinkable" against Barcelona.
Barcelona entered the game leading the series 4-1 on aggregate, but Roma advanced on the away goal tiebreaker after the series finished in a 4-4 tie.
Possibly the two most dramatic minutes in the history of European club football.
Fortunately for Roma, key midfielder Radja Nainggolan has returned from a thigh injury after missing last week's match in Barcelona.
Roma's fans faced an anxious wait after Dzeko was brought down by Gerard Pique in the 58th minute but after a few moments' hesitation, the referee pointed to the spot.
With a three-goal deficit to make up from the first leg, City needed an early goal to give them hope and they got exactly that, taking the lead in the second minute.
Another famous Barca turnaround bookends our run-down.
Barca had an opportunity to hit back less than two minutes later after Juan Jesus tripped the on-rushing Messi 25 yards from goal, but the Argentina forward missed the target with the subsequent free kick.
The Catalan side threw all they had at Roma but their defence stood their ground as the match ended in an emphatic 3-0 scoreline and 4-4 on aggregate as the Italian side qualified into the last four.
Rivaldo then converted a penalty after Celestine Babayaro was sent off and Patrick Kluivert wrapped things up, crushing Chelsea's dreams.