Cerezo Osaka noticed his talent and signed him at the age of 17. He was the first player in Japan to sign a professional contract before graduating from high school, except players promoted from youth teams of the J.League clubs. In 2007, he gained a regular position but the club missed promotion to the J.League Division 1. It was in 2009 that he became the top scorer of J.League Division 2 and drew widespread attention.

Kagawa played as a member of the Japan national under-20 football team in the 2007 FIFA U-20 World Cup held in Canada.

In 2008, he was also selected to play as a member of the Japanese team for the 2008 Summer Olympics.

On 24 May 2008, he made his senior international debut in a friendly Kirin Cup match. Japan won the match against Ivory Coast 1–0. However, was not selected in Takeshi Okada’s final 23 squad for the 2010 FIFA World Cup in South Africa. In September 2010, he scored the only goal of the game in Japan’s win over Paraguay in Yokohama.

On 23 August 2010, he made his debut appearance in the Bundesliga, starting for his new club Dortmund. After scoring his first two competitive goals for the club in the UEFA Europa League qualifying tie against Qarabağ FK, he continued this form with his first goal in the Bundesliga match against VfL Wolfsburg, which Dortmund won 2–0. In the Revierderby against arch-rivals Schalke 04, which Dortmund won 3–1, Kagawa claimed pre-match that he would score two goals; he accomplished the feat, making him a fan favourite in the process.

Kagawa was included in the 2011 AFC Asian Cup by coach Alberto Zaccheroni. In the quarter-final against Qatar, he scored two goals. The game ended in 3–2 win for Japan. In the semi-final against South Korea, Kagawa broke his metatarsal bone and missed the final where Japan beat Australia after extra-time.

On 28 January 2012, Kagawa scored twice in Dortmund’s 3–1 win against Hoffenheim. Kagawa scored the only goal of the game against Werder Bremen on 17 March, heading in a pass from İlkay Gündoğan in the eighth minute. Kagawa scored two goals in Dortmund’s 6–1 thrashing of Cologne on 25 March, keeping Dortmund five points ahead of Bayern in the title race. Kagawa won the Bundesliga with Borussia Dortmund in 2012 as they set a Bundesliga record scoring the most points in a season in the Bundesliga, with 81. Kagawa also scored a goal and provided an assist for Dortmund against rivals Bayern Munich in the 2012 DFB-Pokal Final. He scored a total of 13 goals and had 8 assists during that season.

On 5 June 2012, it was announced by Manchester United that the club had reached an agreement with Borussia Dortmund and Kagawa for his transfer, a deal that made him the first Japanese player to join the club. The fee was reported to be an initial £12 million, with a further £5 million in possible add-ons. The transfer was completed on 22 June after Kagawa passed his medical at Manchester United and received his UK work permit. On 3 July, it was revealed that Kagawa would wear the number 26 shirt for United. Kagawa spoke about his former club, Borussia Dortmund, saying, “I will carry this club, their great fans, and the whole city in my heart forever and will follow their results with great interest.”

On 18 July 2012, Kagawa was handed a two-minute appearance to mark his Manchester United debut in Durban, South Africa, against AmaZulu in a pre-season friendly match. Kagawa made his first start for the Red Devils against Ajax Cape Town on 21 July 2012, and scored his first goal against Shanghai Shenhua four days later. He made his Premier League debut on 20 August 2012, playing the full 90 minutes of United’s 1–0 defeat away to Everton. He scored his first goal against Fulham on 25 August in his home debut for the club. After Tom Cleverley’s shot was parried by Fulham goalkeeper Mark Schwarzer, Kagawa scored on the rebound from close range. On 19 September, Kagawa was given his first Champions League start as United played against Galatasaray. He provided an assist for the winning goal scored by Michael Carrick in a 1–0 win. On 23 October, he set up Javier Hernández for United’s first goal in an eventual 3–2 Champions League victory against Braga. In that match, however, he twisted his knee, which left him sidelined for two months. Kagawa returned from injury in January 2013.

On 2 March 2013, Kagawa scored his first hat-trick for United and also became the first Asian player to score a hat-trick in the Premier League, in his team’s 4–0 home win against Norwich City. On 22 April, Kagawa played a part in the title-winning match against Aston Villa in which United won 3–0; he became the first Japanese player to win a Premier League title. On 12 May, Kagawa was included in the United squad to play against Swansea City in Alex Ferguson’s last home game before retirement, which United won 2–1. On the same day, Kagawa received his Premier League medal and was voted Man of the Match.

On 31 August 2014, Kagawa officially returned to his former club, Borussia Dortmund, for an undisclosed fee thought to be around £6.5 million and signing a contract until 30 June 2018. He was assigned the shirt number 7 which was vacated by Jonas Hofmann who had left Dortmund to 1. FSV Mainz 05 on loan. On his return debut, Kagawa scored a goal and set up another to help Dortmund win 3–1 against SC Freiburg.

Kagawa was named in Japan’s 23-man squad for the 2013 FIFA Confederations Cup and scored the second goal for his country during the group stage match against Italy, which ended in a 4–3 loss. He was selected for his first World Cup in 2014, but made little impact as the “Samurai Blue” was eliminated at the group stage.

At the 2015 AFC Asian Cup, Kagawa scored Japan’s second goal during a 2–0 defeat of Jordan in the group stage and was named as man of the match.

On 14 July 2017, Kagawa extended his contract with Dortmund until 2020.

On 9 August 2019, Kagawa completed a transfer to Real Zaragoza of Spain’s Segunda División, penning a two-year contract. He debuted for the club on 17 August 2019, in the 2019–20 Segunda División opening match against Tenerife at La Romareda, which Zaragoza won 2–0. Eight days later, he scored his first goal in a 1–1 draw against Ponferradina.

On 2 October 2020, Kagawa’s contract was terminated by Zaragoza.