On 17 January 2021, Giuliano Simeone made his senior debut with Atlético Madrid's B-team, scoring the opener in a 1–1 draw against UD Poblense in Segunda División B.
In 2021, Giuliano Simeone returned to Atlético Madrid B, now in Tercera División RFEF, and scored eight goals in 11 matches between November and December.
On 4 July 2022, Giuliano Simeone was loaned to Segunda División side Real Zaragoza for the season.
On 21 July 2023, Giuliano Simeone renewed his contract with Atlético Madrid until 2028 and moved on loan to Deportivo Alavés for one year.
On 19 November 2024, Giuliano Simeone debuted for Argentina against Peru in a 2026 FIFA World Cup qualification, becoming the second son of Diego Simeone to play for Argentina.
In 2024, Giuliano Simeone competed for Argentina at the Summer Olympics.
On 29 January 2025, Giuliano Simeone scored his first Champions League goal and provided an assist in a 4–1 away win over RB Salzburg.
On 25 March 2025, Giuliano Simeone scored his first goal for Argentina in a 4–1 victory against Brazil in a 2026 FIFA World Cup qualification match.
On 15 January 2026, Giuliano Simeone extended his contract with Atlético Madrid until 30 June 2030.
On 21 July 2023, Giuliano Simeone renewed his contract with Atlético Madrid until 2028.
On 15 January 2026, Giuliano Simeone extended his contract with Atlético Madrid until 30 June 2030.
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