Wounded from a crushing defeat to Real Madrid in the Spanish Super Cup, the Catalan giants ensured that they would start their league season with all three points courtesy of two goals in the first half of action.
As for Betis, Victor Camarasa, Sergio Leon, Zouhair Feddal, Andres Guardado, Juan Jose Narvaez and Antonio Barragan all made their debuts for the Seville outfit. There was also a position in the team for Joaquin, but fellow new arrivals Jordi Amat and Javi Garcia started on the bench.
Barcelona had a decent chance to make the breakthrough inside three minutes when Roberto drove into the Betis box before feeding Deulofeu in a dangerous area, but the Spaniard poked the ball wide of the post.
Messi was next to come close for the hosts in the 14th minute after winning a free kick in a dangerous position, but the Argentine's set piece just landed on the top of the Betis net, before Deulofeu had a goal-bound strike blocked three minutes later after a mistake from Betis goalkeeper Antonio Adan.
Messi had another opportunity in the 25th minute after collecting a Busquets pass just inside the Betis box, but the attacker's low effort just curled wide of the post as the score remained goalless.
Betis were without the ball for much of the opening 30 minutes, but the visitors were dangerous when they had the chance to break, with Joaquin rolling back the years with some wonderful touches in the final third of the field.
Barcelona looked to have made the breakthrough in the 35th minute when Messi curled a sensational free kick towards the bottom corner, but the ball rebounded off the post as Betis survived another dangerous moment.
The home side finally opened the scoring in the 36th minute, however, when Betis defender Alin Tosca turned a low Deulofeu cross into the back of his own net under pressure from Messi.
The visitors should have been level two minutes later when Leon broke into the Barcelona box, but Javier Mascherano came from nowhere to make a wonderful challenge, and the resulting counter-attack saw the Catalan outfit move 2-0 ahead as Roberto swept a Deulofeu cross into the back of the net.
The first 10 minutes of the second period passed without incident. Deulofeu continued to cause problems in a wide position, although Betis were quite comfortable as they looked to stay in the contest.
Messi hit the woodwork once again in the 60th minute after curling a beautiful effort towards the bottom corner, with the Argentine again lighting up Camp Nou in the absence of Luis Suarez and Neymar.
Deulofeu and Alcacer were not quite the support act that Messi has become accustomed to in recent seasons, but the former ended what was an emotional night for Barcelona with two assists.
Nahuel Leiva had a decent opportunity to halve the deficit 20 minutes from time after finding space just outside the Barcelona box, although the on-loan Villarreal winger missed the target with a wild attempt.
Aleix Vidal was next to come close for Barcelona after a super Messi pass freed the substitute inside the Betis box 15 minutes from time, but he could not find a route past Adan in the away side's net.
Messi hit the woodwork for a third time in the 81st minute as a thumping effort rebounded off Adan's post, and the 30-year-old could afford a slight smile on what was a frustrating evening for the stand-in captain.
Next up for Barcelona, who hope to announce the signing of Ousmane Dembele from Borussia Dortmund next week, is a trip to Alaves next Saturday, while Betis will host Celta Vigo one day earlier.