Isco represented Spain at various youth levels, including at the 2012 Olympics, and made his senior international debut in 2013, later taking part at the 2018 FIFA World Cup.

[4] A product of Valencia's youth system, he spent the 2009–10 season with the club's reserve team in Segunda División B, netting once in 26 games and suffering relegation.

[9][10] In mid-July 2011, Isco moved back to his home province and signed a five-year contract with Málaga after the club activated his buy-out clause of €6 million.

On 18 September 2012, in Málaga's first game in the Champions League group stage, Isco netted twice in a 3–0 home win over Zenit, also being chosen as Man of the Match.

[18] He scored his eleventh goal of the campaign on 13 March, netting the opener in a 2–0 home win against Porto, good enough for last-eight qualification after the 0–1 first leg loss at the Estádio do Dragão.

[25] In spite of continuing to score regularly when featured, Isco received limited opportunities in the first team due to the 4–3–3 formation not being suited for his style, but Ancelotti stated that it was "a temporary problem".

[26] He scored 11 goals in 53 official games in his first season, including 61 minutes in the Champions League final, a 4–1 win over Atlético Madrid in Lisbon.

[33] Isco was a part-time starter when the team won the 2015–16 UEFA Champions League defeating Atlético Madrid 5–3 on penalties in the final played at the San Siro in Milan, Italy.

However, on 31 January 2023, the deal collapsed, despite him passing medical tests, as the German club claimed that he made new demands that differed from the original agreement.

In 2011 he represented his country – together with Málaga teammate Recio – in the U-20 World Cup held in Colombia, netting one goal in an eventual quarter-final exit.

[55] Also that year he appeared at the UEFA European Under-21 Championship in Israel, he scored in the final and finished the competition with the Bronze Boot (3 Goals) and made the team of the tournament as a key player for the eventual winners.

[63] Following his move to Real Madrid, manager Carlo Ancelotti also played him in a deep-lying playmaker role requiring more sacrifice and defensive duties than his natural position.

[64] A quick, skillful and creative player, with excellent technique and ball control, Isco is known for his natural ability to pick out an inch-perfect pass, dribble effortlessly through two or three challenges or drift a shot into the top corner of the goal.

In 2013, Isco was credited by Marca journalist Pablo Polo as being "the most promising young player in Spanish football", comparing his strength, skill, and low centre of gravity to Sergio Agüero, and his vision and passing abilities to Zinedine Zidane.