Two own goals - one each side of half-time - put the Giallorossi in a difficult position and, despite creating a handful of good openings, things looked difficult when Gerard Pique tapped home on the hour-mark.
Edin Dzeko then fired home from close range with ten minutes remaining to give Eusebio Di Francesco's side a lifeline, only with Luis Suarez's late finish to put an entirely slant on the scoreline.
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The Giallorossi will look back with some pain at two first-half penalty shouts that appeared to have plenty of merit, while early in the second half - with the score still just 1-0 - Diego Perotti was presented with a glorious headed opportunity that he steered narrowly wide.
The two sides will reconvene at the Stadio Olimpico in six days' time for the second leg - with Roma needing to score three times to have any hope of progressing.
Radja Nainggolan was ultimately deemed not to be fit enough to take part in the game, so Lorenzo Pellegrini came into central midfield alongside Daniele De Rossi and Kevin Strootman.
Elsewhere coach Eusebio Di Francesco sprang something of a surprise, as he opted for both Bruno Peres and Alessandro Florenzi in the side - with Peres at right-back and Florenzi pushed further forward.
In attack, Diego Perotti joined Edin Dzeko.
7' - Lively start at the Camp Nou. Suarez thinks he has broken the deadlock, but the flag is up and the celebrations are short-lived.
10' - Penalt.... no! Dzeko is clumsily knocked down by Semedo inside the box as he tries to shoot... but the referee waves away the claims!
11' - Messi goes for goal from 25 yards; it's a powerful effort, but Alisson is able to palm it away and then claim the loose ball.
18' - Barcelona hit the post! Rakitic steers in a low inswinging cross that eludes everyone before hitting the outside of the post and bouncing clear! Suarez blasts wide the follow-up effort...
24' - Florenzi tries to play in Kolarov on the counter, but Barca win the ball back and launch a counter of their own. Messi is eventually stopped as he harries into the box.
28' - Big save from Alisson! The goalkeeper gets down sharply to his left to parry away Suarez's low drive...
38' - Goal. Barcelona take the lead. De Rossi stretches to intercept Iniesta's pass and inadvertently puts the ball in his own net. 1-0.
41' - Roma win a free-kick on the edge of the box. Pellegrini's curling effort is blocked by the wall and Barcelona clear the danger.
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46' - Immediate chance for Roma! Florenzi swings in a perfect cross for Perotti at the far post, but the winger cannot plant his header on target!
49' - Florenzi goes for a snapshot from the edge of the box but drags his effort wide.
56' - Goal. Barcelona double their advantage. Another own goal, this time Manolas the unfortunate party as his attempt to cut out the cross hits the post, comes back, hits him and goes in. 2-0.
60' - Goal. Barca score. Alisson saves Suarez's effort but it falls perfectly for Pique to tap home. 3-0.
74' - Perotti bursts forward into the box and then cuts the ball back for Strootman, whose powerful shot is deflected away for a corner.
77' - Ter Stegen gives the ball away in a dangerous area and Perotti feeds Defrel for an immediate chance - but the 'keeper recovers to make an important block!
79' - Another save from Ter Stegen! This time he dives full stretch to his left to tip away Perotti's inswinging effort!
80' - GOAL! ONE BACK! Vital goal! Perotti fires in the low cross that Dzeko gathers perfectly before passing a low shot inside the near post from 10 yards out. Daje! 3-1.
86' - Goal. Barcelona score. Suarez pounces on the loose ball inside the box and drives home. 4-1.
89' - Kolarov curls narrowly over from a free-kick in a dangerous position. Good opportunity
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“I think the result is unfair on us given the way we played against a team like this. We scored an incredible own goal – Daniele De Rossi's – and made mistakes in our own area. We made a game of it but were too slow in dropping off and reading certain situations. Ultimately, we needed to score when we had the chance to do so, like through [Diego] Perotti at the start of the second half or when we won the ball off their keeper. We needed to be more clinical because Barcelona are unforgiving.”
- Eusebio Di Francesco
“The penalty could have changed the game. The referee needs to have the courage to give a penalty against Barcelona, because we are also in the quarter-finals and all of the teams here have earned the right to play.”
- Edin Dzeko
The Giallorossi have one Serie A engagement between now and the second leg at the Stadio Olimpico - as they host Fiorentina on Saturday afternoon.
That game actually kicks off a run of three straight matches at the Olimpico for Di Francesco's side - with Barcelona arriving on Wednesday, and then arch-rivals Lazio 'hosting' them in the derby the following Sunday.
Goalscorers: De Rossi o.g. (38'), Manolas o.g. (55'), Pique (59') Suarez (87'); Dzeko (80')
Barcelona: Ter Stegen; Semedo, Pique, Umtiti, Alba; Roberto, Rakitic, Busquets, Iniesta; Messi, Suarez.
Roma: Alisson, Peres, Manolas, Fazio, Kolarov; Strootman, De Rossi, Pellegrini; Florenzi, Dzeko, Perotti.
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