Luis Suarez scored twice as Barcelona produced a polished performance to leave Manchester City's Champions League hopes hanging by a thread at the Etihad Stadium.
Suarez capitalised on captain Vincent Kompany's error to slam the visitors ahead before toe-poking Jordi Alba's cross into the corner prior to half time as City were outclassed during the first 45 minutes.
Sergio Aguero gave the Premier League champions hope as they staged a second half revival but their good work was undone when Gael Clichy was sent off for a second booking after fouling Dani Alves.
Lionel Messi should have added to the Barcelona lead in added on time but saw Joe Hart save his penalty after Pablo Zabaleta brought down his fellow-countryman, but the final act did little to take the gloss off a complete Barca performance.
The result requires City to score at least twice come the second leg at the Nou Camp in three weeks time, a giant challenge against a Barcelona side who made a mockery of their tag a tournament dark horses.
Despite putting five past Newcastle United on Saturday and going within five points of leaders Chelsea, Manuel Pellegrini was without the influential Yaya Toure, whom they had won just twice without during the recent Africa Cup of Nations.
Aguero, absent from both legs of 4-1 aggregate loss to the Catalans in last term's round of 16 clash, led the attack in an offensive City starting eleven following their plucky route into the knock-out phase, with Edin Dzeko also included.
Malaga might have ended Barca's 11-match winning run at the weekend, which allowed Real Madrid to pull four points clear in the La Liga title race, but Luis Enrique's side arrived in the North West in buoyant mood having survived their early season crisis of confidence.
Summer recruit Suarez bolstered a three-pronged forward line led by Neymar and Messi, who was looking to further enhance his status as the Champions League's leading scorer.
Though playing in their fourth straight season in the continent's premier club competition, City had been dogged by nerves ever since their first foray into top tier European football, and their uncertainty was prevalent again as Barca took control early on.
Kompany cleared agonisingly wide of his own goal and Messi was denied by a last ditch tackle after Neymar jinked inside Pablo Zabaleta as the visitors dominated the early stages, and it came as no surprise when the opening goal came after 16 minutes.
Messi's cross from the right was flicked on by Suarez and when Kompany couldn't clear, merely allowing the ball to rebound off him in the penalty area, the Uruguay international reacted first and slammed past Hart.
The England goalkeeper denied the former Liverpool striker a second but it didn't take long for Suarez to double his tally as City folded in the first half. After the majestic Ivan Rakitic fed Messi, the Argentine glided through three players, found Jordi Alba, whose cross was poked in by Suarez.
Alves chipped Hart but hit the bar in the closing moments of the first half as Enrique urged his team forward in search of further goals, as City held a watching brief as their Champions League lives flashed before their eyes.
Chances at the start of the second half at least suggested City could make the remainder of the tie, if not the return match at the Nou Camp, competitive, first as Javier Mascherano blocked from Samir Nasri, before Dzeko inexplicably planted a header at Ter Stegen from six yards.
Aguero shot wide after wriggling away from Mascherano and Martin Demichelis nodded straight into the arms of Ter Stegen as the opportunities continued to be squandered and with it, routes for a way back into the tie.
Wilfried Bony came on for the final quarter of the game and his introduction saw City get a foothold as Fernando fed Silva, whose flick around the corner was taken on by Aguero who got beyond Gerard Pique and smashed home.
But just as Barcelona looked on the rack for the first time in the tie, City were left playing survivors once again as Clichy, already booked and out of the second leg in a fortnight's time, was cautioned again for a high foul on Alves and dismissed.
The red card ended any hope of City restoring parity ahead of the second leg, and it could have been worse had Hart not beaten out Messi's stoppage time spot kick, and leaves them with a mountain to climb to maintain their interest in the Champions League beyond the last 16.