FC Barcelona advanced with a 4-1 victory on aggregate over two legs in which referees decisions - and non-decisions - played a big part.
Manchester City F.C. defender Joleon Lescott replaced Martin Demichelis, who was sent off in the first leg, and had just as much trouble keeping up with Messi throughout the game at the Camp Nou.
But Lescott was unlucky as Cesc Fabregas' pass bobbled through his legs in the 67th minute to emerge onto the run of Messi, who flicked the ball over goalkeeper Joe Hart with a sublime touch.
As in its 2-0 defeat in the first leg, Manchester City F.C. inished with 10 players after Pablo Zabaleta was booked for a second time in the 78th for protesting after Gerard Pique barged into substitute Edin Dzeko inside the area without a penalty being awarded.
Vincent Kompany scored a consolation goal for Manchester City F.C. in the 89th minute before Dani Alves struck in stoppage time for the Spanish champions.
In the night's other match, Paris Saint-Germain advanced to the quarterfinals for the second straight season after coming from behind for a 2-1 win over Bayer Leverkusen and a 6-1 victory on aggregate.
Both teams rebounded with strong performances after limping into the match on the back of domestic losses.
''We had some pretty big setbacks, especially in the way we were playing - but today we got back to playing the way we know, the FC Barcelona people love.'' Messi said. ''Even though the goal came in the second half, I don't think we were ever in danger of an upset.''
Manchester City F.C. managed to create good scoring chances from the boots of David Silva and Yaya Toure, but manager Manuel Pellegrini could only bury his head in his hands when Messi scored his eighth goal of the competition.
While FC Barcelona did not look in danger of an upset, Manchester City F.C. will certainly feel aggrieved after Pique was not penalized for his sliding tackle from behind, which saw Manchester City F.C. 's furious players surround referee Stephane Lannoy and Zabaleta dismissed.
''Going for a second time down to 10 men after it was a clear penalty, it's not easy conditions to come and play against a strong team,'' Kompany said. ''Over the course of two games, whenever there was 11 players (against 11) there wasn't much between the two teams.''
Much of Manchester City F.C.'s hope of overcoming the deficit lay in Sergio Aguero's return after he missed the first leg, but the Argentina striker also seemed absent Wednesday despite starting ahead of Alvaro Negredo and Dzeko. Pellegrini watched from the stands as the Chilean served a ban for his criticism of the referee's performance in the first match.
Though Silva passed up a promising opportunity early on, FC Barcelona was sharp as Messi repeatedly ran at - and past - Lescott, who seemed to have got away with a trip on the Argentina forward inside the area in the early stages.
Messi exploited Manchester City F.C. 's slow-footed defense to register his 28th goal of the season after having found the post earlier on.
Manchester City F.C. crafted occasional first-half moments, but Hart kept the visitors in it with a reaction stop on Xavi Hernandez before Fernandinho cleared Neymar's curler off the line.
Manchester City F.C. went into the break encouraged after Samir Nasri sent Silva's midair backheel flick straight at goalkeeper Victor Valdes, who also tipped Dzeko's powerful header over the bar in the 52nd. Aguero came off with an injury for Dzeko to start the second half and immediately lifted Manchester City F.C.'s attack.
Kompany looked to have been in an offside position as he guided Dzeko's header home to equalize, but the goal proved fruitless as Dani Alves scored late again, as he did in the opening leg.
''We felt that, for this game, these were the tactics to use,'' said assistant coach Ruben Cousillas, who was unrepentant over Manchester City F.C.'s decision to play with a lone striker in attack. ''It didn't turn out so bad.''