Antoine Griezmann, Pedri and Ousmane Dembele also scored for Barca while Antonio Sanabria and Loren Moron replied for Betis, who had Aissa Mandi sent off on the hour-mark.
Barca’s first league victory since beating Celta Vigo on Oct. 1 took them into eighth in the table with 11 points from seven games. Real Sociedad lead the standings with 17.
Barca’s captain was surprisingly left out of the starting line-up by coach Ronald Koeman, who later explained that Messi was feeling a little discomfort after the 2-1 win over Dynamo Kyiv in mid-week and had agreed to start on the bench.
Koeman’s side played well in the first half without Messi but missed a slew of clear opportunities and found themselves drawing 1-1 when Sanabria cancelled out Dembele’s superb opening strike on the stroke of halftime.
Messi was brought on at the start of the second period and promptly produced a sublime dummy to allow Griezmann to tap into an unguarded net and put Barca back in front in the 49th minute, the Frenchman finally making amends for missing four chances before the break including squandering a penalty.
- READ MORE
- Barcelona reach Copa del Rey final with epic comeback win over Sevilla
- GOAT? Juventus talisman Cristiano Ronaldo's scoring records
- Arsenal manager Arteta speaks on his Barcelona links
- Barcelona, Atletico ordered to further tighten belts by La Liga
- What is Barcagate? All you need to know about Barcelona scandal
- Barcelona CEO and former president Josep Maria Bartomeu arrested
Barca’s all-time top scorer Messi then further stretched their lead in the 61st by emphatically dispatching a penalty after Aissa Mandi was shown a straight red card, following a VAR review, for using his arm to block a shot from Dembele.
“The whole squad prefers it when Messi is on the pitch because he obviously gives you more options to win the game,” said Barca’s Jordi Alba.
“Today he came on and changed the game, he is a different player to everybody else and we were a different team when he was on the pitch.”
Koeman added: “He would have started if he hadn’t had any discomfort. We all know who he is and I don’t have any doubts about him, I see him work every day. He didn’t start but he was very important in the second half.”
Betis did manage to pull a goal back with 10 men when striker Loren netted at the far post to make it 3-2 after a marauding run down the left wing by Alex Moreno.
But Messi soon put the game beyond doubt, smashing the ball into the top corner after receiving a wonderful backheel from team mate Sergi Roberto, while 17-year-old Pedri struck the fifth after another fine pass from Sergi Roberto.
“The manager made a decision to not start him and in the second half he really helped us to go on and win the game,” added Alba.
“We all prefer it when he is on the pitch, we’re better with him around.”