Ramos made his professional debut with Sevilla FC in 2004. He played one season for the club, making 41 appearances and scoring two goals.

Ramos joined Real Madrid in 2005 for a then-record fee of €27 million. He quickly established himself as a key player, playing mainly as a center-back but also occasionally as a right-back. Over 16 years, he won numerous domestic and international titles, including five La Liga titles and four UEFA Champions League trophies.

Ramos signed a two-year contract with Paris Saint-Germain in July 2021. He won two Ligue 1 titles during his time at the club, although his form was often questioned and his departure at the end of the 2022/23 season was not seen as a surprise.

Ramos returned to Sevilla FC after his stint with Paris Saint-Germain, marking an emotional return to his hometown club.