Alex Pozuelo scored in the 54th minute and substitute Roque Santa Cruz added a second in stoppage time to give Betis a second straight victory and boost its own beleaguered coach, Pepe Mel. Pozuelo was sent off in the 72nd.
Atletico are without an away win in seven Spanish league matches but their impressive home form had given Manzano some protection.
This latest defeat leaves the Atletico coach in an increasingly precarious position. Atletico has a Copa del Rey fixture against third-tier Albacete on Thursday, aiming to overturn a shock 2-1 defeat in the away leg.
With the Christmas break approaching, anything but a win against Albacete looks likely to end Manzano’s time at the club he took over for a second time in June.
Atletico started brightly against Betis, with striker Radamel Falcao spurning two early opportunities—first glancing a third-minute header wide when he should have scored, then hooking a volley round the post in the sixth.
Atletico winger Arda Turan saw his back-post volley pushed away by Betis goalkeeper Casto Barriga in the 44th, but the visitors improved in the second half.
Pozuelo controlled a pass from Ruben Castro before advancing past Alvaro Dominguez and firing into the roof of the net to open the scoring.
Pozuelo got a second yellow card for handling the ball in the 72nd, but Atletico failed to find an equalizer despite heavy pressure.
Barriga produced a flying one-handed save to keep Adrian’s header out of the net in the 75th and Santa Cruz scored Betis’ second after following up his own shot that hit the crossbar in the 91st.
Later Sunday, third-place Valencia host European hopeful Malaga, while Osasuna receive Villarreal, Real Sociedad go to Racing Santander and Levante visit Granada.
On Saturday, a hat-trick from Cristiano Ronaldo inspired Real Madrid to a 6-2 romp at Seville to lead Barcelona by three points atop the standings.
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