Manchester City were left to concentrate on their title challenge as their Champions League campaign ended in defeat in Barcelona.
In another clash overshadowed by refereeing controversy, City had Pablo Zabaleta sent off as they were beaten 2-1 in the Nou Camp to go out 4-1 on aggregate at the last-16 stage.
City captain Vincent Kompany did briefly level the scores at 1-1 in the closing minutes but it proved a mere consolation.
For a spell City troubled the Spanish champions but could not find the goal that would change the tie. Samir Nasri had a good chance in the first half while substitute Edin Dzeko brought a good save out of Victor Valdes.
But, in truth, Barca should have been in the lead long before Messi finally struck with a neat dink, after pouncing on a Joleon Lescott error, in the 67th minute.
Lescott had been fortunate not to concede a penalty after felling Messi early in the match and City also breathed again when a Neymar goal was harshly disallowed for offside.
City were on the wrong end of a decision from referee Stephane Lannoy themselves when Dzeko was denied a penalty after being clipped by Gerard Pique.
Zabaleta was sent off for protesting in the arguments that followed.
The result saw City eliminated from a second competition in the space of three days after Sunday's FA Cup loss to Wigan.
Attention now turns to the Premier League, in which they trail Chelsea by nine points with three games in hand.
Kompany said: "If anything, it should give us motivation. The way we played against Wigan, the performance was completely different. Only the winners get remembered, but it's only the third year ever for Manchester City in the Champions League. I'm looking at this and I don't see why next year we should fear anyone.
"I think I speak for the team in saying we've got nothing left in the tank."