Spain international Xavi, the first Barca player to reach the 400 milestone, clipped the ball high into an empty net in the 10th minute at the Nou Camp after a Cesc Fabregas shot had ricocheted back off a post.
Pep Guardiola's side were cruising when Messi added a second two minutes later but Barca conceded their first league goals at home this season when a battling Betis struck either side of the break to make it 2-2.
"We managed to get through a very tough game," Xavi, a youth academy graduate who made his debut under former coach Louis van Gaal in a Spanish Super Cup game in August 1998, said in an interview with Spanish television.
"Betis also want the ball and they played well and made things pretty difficult for us," added the 31-year-old, who finished behind Messi in Monday's FIFA World Player of the Year awards.
"Their players have a lot of technical ability and that's why it was an open game with chances for both sides."
Barca's home form has been almost impeccable, winning nine and drawing one of their 10 games and scoring 43 goals and conceding two.
Real's success in Mallorca was a club record 11th straight victory away from home in all competitions and they host Barca, whom they beat 1-0 in last year's final, in a King's Cup quarter-final first leg on Wednesday.
"We'll try to recuperate in the next few days so we can go to Madrid and play the best match possible," Guardiola said at a news conference.
"It's always better coming into a match having won the previous game, always," he added.
Marcelo Bielsa's side climbed to fifth on 26 points, level with Osasuna but ahead on goal difference after the Pamplona-based club lost 2-0 at home to Racing Santander, their first defeat in seven games.
