Born in Sabadell, he joined the Barça youth system in the summer of 2005 from Jabac. That season, playing for the U19A side, he won three major trophies alongside the likes of Bojan Krkic, Giovani, Jeffren and Marc Crosas. 

The following season, Busquets moved up to Barça B under coach Pep Guardiola, making 23 appearances, scoring twice, and making a major contribution to the promotion to Division 2B. He appeared for the first team in the Copa Catalunya matches of 2007-08 and 2008-09, and gradually Busquets would get more and more chances as the season drew on, and was very much involved in the famous treble winning season. 

In the 2009-10 season, he established his name as one of the most talented central midfielders on the international scene. The following seasons saw him consolidate his reputation as the man who makes Barça tick in the middle of the park as the trophies kept on coming, highlights being his 3 Champions League winners' medals and 8 league titles. With the departures of Andrés Iniesta and Leo Messi, Busquets assumed the role of club captain. Together with Gerard Piqué, he is third on the all time list of trophy winners in FC Barcelona history. 

His fine form for Barça has won him international recognition. He played his first game for Spain on April 1, 2009, at the Ali Sami Yen, against Turkey (1-2). He also played in the 2009 Confederations Cup in South Africa. Vicente del Bosque used Busquets as a starting midfielder in the side than won the country’s first World Cup in South Africa in 2010, and he also starred in the successful defence of the European Championship crown in 2012 . Busquets and Spain were runners-up at the 2013 Confederations Cup in Brazil and in Spain’s less successful bid to retain the World Cup in Brazil in 2014. Busquets also played in Euro 2016 in France, Euro 2020 and the 2018 World Cup in Russia. In 2022 he took part in the World Cup in Qatar with Spain after which he announced his retirement from international football. 

During the 2021/22 season, he surpassed Andrés Iniesta to become the third player with the most appearances in Barça's history.