Valverde was looking vulnerable after just one win in four, a run which saw Real Madrid draw level with them on points at the top of the Spanish league table.
There was also talk of unrest from the club’s hierarchy and fans for the style of football being played under Valverde, which also led to his exit.
The 55-year-old took training on Monday morning amid intense speculation his time as coach was about to come to an end and his fate was sealed later in the evening.
The former Athletic Bilbao and Espanyol manager has guided Barca to LaLiga titles in each of his two full seasons in charge, as well as winning the Copa del Rey and Spanish Super Cup in 2018.
Barca thanked Valverde “for his professionalism, his commitment, his dedication and his always positive treatment towards all that make up the Barca family”.
Former Real Betis boss Setien was named as Valverde’s successor soon after, on a contract until June 2022.
Setien has made a name for himself with a unique possession-based style of play, something which could bring the type of football back to Camp Nou that the fans have been used to over the years.
Barcelona legends Xavi and Ronald Koeman are both thought to have been contacted about taking up the position, but with both unwilling to step in just yet Barca have looked elsewhere.