Ex-Valencia player Sergio Canales opened the scoring for Manuel Pellegrini's Betis in the 19th minute, Cristian Tello bagging the second in the 74th, both goals aided by decisive passes from tireless 39-year-old Joaquin.
Atletico Madrid could only manage a goalless draw with Villarreal, who were leapfrogged into second on goal difference by Real Sociedad, 3-0 winners over Getafe.
Mikel Oiarzabal opened the scoring for Real Sociedad with a 28th-minute penalty, before Mikel Merino and Portuguese midfielder Portu bagged a quick goal each with 10 minutes to play.
Real Madrid travel to Levante and Barcelona host Sevilla in the knowledge that the head of the table could change depending on results.
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