[citation needed] On 8 March 2012, at the age of just 17 years and 108 days, he made his debut with the Atlético first team, playing the last six minutes of a 3–1 home win against Beşiktaş in the UEFA Europa League.

[13][14] In a Madrid derby on 7 February 2015, Saúl replaced the injured Koke after ten minutes, and scored his team's second goal shortly after through a bicycle kick, in a 4–0 win.

[15] From the 2015–16 season onwards, after the departure of Mario Suárez and the injury of Tiago Mendes, Saúl became a nuclear midfield element for the Diego Simeone-led team.

[16][17] On 27 April 2016, Saúl played 85 minutes in the first leg of the semi-finals of the UEFA Champions League against FC Bayern Munich, and also scored the only goal at the Vicente Calderón Stadium with an individual effort.

[25] In the 2020 Supercopa de España Final against Real Madrid, which ended 0–0 after extra time, both he and Thomas Partey missed their shoot-out attempts in a 4–1 defeat.

[30] On 30 June 2020, Saúl scored twice from penalties in a 2–2 draw away to Barcelona, as Atlético managed that number of goals against that opposition in a league match for the first time under Simeone.

[33] He won the Club World Cup with Chelsea on 12 February 2022, coming on as a 76th minute substitute to replace Callum Hudson-Odoi in a 2–1 final victory against Palmeiras.

[38] On 26 May 2015, Saúl was called to the senior team for a friendly with Costa Rica and a UEFA Euro 2016 qualifying match against Belarus,[39] but did not make his debut on either occasion.

[45] Under new coach Luis Enrique, Saúl scored his first goal for his country on 8 September 2018, equalising in an eventual 2–1 win against England for the 2018–19 UEFA Nations League A at Wembley Stadium.

[45] Following Luis Enrique's appointment as Spain manager in 2018, Diario AS' Alfredo Relaño remarked that "Saúl is the player to move the ball forward with purpose and attempt to finalise long passages of possession", adding that "The new centre of the park for Spain (where so much happens for the national side) is now defined by him, a box-to-box player and one never afraid to try his luck in front of goal",[47] Sid Lowe of The Guardian opined that "now he embodies the shift, technique and talent but athleticism too, blessed of impeccable timing, arriving in the area".