Born on 27 June 2004 in Alicante, Spain, to Colombian parents, Cristhian Mosquera began his footballing journey at Hércules CF before joining Valencia CF's academy at the age of 12 in 2016. He rose quickly through the youth ranks and made his first-team debut in January 2022, starting Valencia's Copa del Rey win over CD Atlético Baleares at just 17. Days later, he made his La Liga debut against Sevilla, becoming the fourth-youngest player ever to represent Valencia in the top flight — a list that includes Ferran Torres and Lee Kang-in.
Mosquera spent the following seasons establishing himself as a first-team regular at Valencia, scoring his first professional goal in a 2–0 La Liga win over Leganés in February 2025. On the international stage, he was part of the Spain U23 squad that won gold at the 2024 Paris Olympics, one of the standout honours of his career to date.
A composed centre-back with pace, good anticipation, and the technical ability to play out from the back, Mosquera can also operate as a full-back on either flank.
In July 2025, Arsenal signed him on a long-term deal for a reported fee of around £13 million, with the club viewing him as a key part of their defensive future. He marked his debut with a substitute appearance in a 5–0 home win over Leeds United and quickly demonstrated his value, starting a 3–0 victory over Nottingham Forest shortly after. Arsenal reached the EFL Cup final in 2025–26, finishing as runners-up.