Oxlade-Chamberlain joined the Southampton Academy at the age of seven. On 2 March 2010, he made his first-team debut for Southampton, at 16 years 199 days, coming off the bench in a 5–0 victory over Huddersfield Town and became the club’s second youngest ever appearance maker behind Theo Walcott. Oxlade-Chamberlain appeared as an 82nd-minute substitute for Jason Puncheon on 8 May 2010 in the final match of the season against Southend United. At the beginning of the 2010–11 season, Oxlade-Chamberlain made his first competitive start on 10 August against AFC Bournemouth in the first round of the League Cup. During the match, he scored the second goal of Southampton’s 2–0 victory, his first senior goal.

On 20 August 2010, shortly after his 17th birthday, Oxlade-Chamberlain signed his first professional contract lasting for three years. His first league start came in a 2–0 loss at home to Rochdale on 4 September 2010. His first league goal came in a 2–1 victory over Oldham Athletic on 23 October 2010, which proved to be the match winner. He scored two more goals and also got an assist in a 4–0 win over Dagenham & Redbridge on 2 November 2010, when he was voted Man of the Match in a league match for the first time.

Oxlade-Chamberlain was called up to the England Under-18 squad for the match against Poland which took place on 16 November 2010 at Adams Park. England won the match 3–0 and Oxlade-Chamberlain played the first 45 minutes before he was substituted.

On 8 August 2011, Oxlade-Chamberlain signed for Premier League club Arsenal. Although neither club involved revealed details of the contractual arrangements, press sources indicated that the fee was a £12 million initial payment which could rise to £15 million with “add-ons”.

On 28 August 2011, he made his Arsenal debut in the 8–2 defeat away to Manchester United, as a 62nd-minute substitute for Francis Coquelin, thus becoming the 150th player to represent Arsenal in the Premier League. On 20 September 2011, he scored his first goal for Arsenal in the 58th minute of a League Cup match against Shrewsbury Town, with a drive from 25 yards. Arsenal won 3–1.

On 28 September 2011, Oxlade-Chamberlain scored the opening goal in the eighth minute of his UEFA Champions League debut against Greek team Olympiacos, running diagonally onto an Alex Song long pass and past several defenders before finishing into the corner of the goal. In so doing, he became the youngest Englishman to score in the Champions League, surpassing teammate Theo Walcott’s record.

He was called up to the England Under-19 squad to face Germany on 8 February 2011, but on 2 February he was promoted into the England under-21 team for a friendly match away to Italy on 8 February. In the match, he came on as a 60th-minute substitute, replacing Henri Lansbury. England lost the match 1–0 with the Italians scoring from a penalty two minutes from time.

Oxlade-Chamberlain made his first start for the Under-21s against Azerbaijan on 1 September 2011 and claimed two assists during the game. He also made a brief appearance against Israel on 5 September, coming on in the second half to claim three assists (including winning a penalty) to push England from a 1–0 deficit to a 4–1 comeback victory. A month later, he scored a hat-trick against Iceland as England won 3–0 in Reykjavík. On 10 November 2011, Oxlade-Chamberlain played in 5–0 win for the under-21s against Iceland, to remain top of Group 8. On 29 February 2012, he netted a late penalty as England made certain of at least a play-off spot for the 2013 UEFA European Under-21 Championship with a 4–0 victory over Belgium.

Oxlade-Chamberlain started his first Premier League match for Arsenal in a 2–1 defeat to Manchester United at the Emirates Stadium on 22 January 2012, contributing an assist to a Robin van Persie goal. Arsène Wenger replaced him with Andrey Arshavin in the 78th minute, with the score at 1–1. Not only did Arsenal fans boo the decision to take Oxlade-Chamberlain off, Van Persie also remonstrated with the manager. On 4 February 2012, Oxlade-Chamberlain celebrated his first two Premier League goals in a home match against Blackburn Rovers which finished in a 7–1 victory to Arsenal. Following this match, Wenger praised Oxlade-Chamberlain for his fast development.

On 19 December 2012, it was announced that Oxlade-Chamberlain, along with teammates Aaron Ramsey, Kieran Gibbs, Jack Wilshere and Carl Jenkinson, signed a new long-term contract with Arsenal. Oxlade-Chamberlain scored his only Premier League goal of the 2012–13 season in a 7–3 home win against Newcastle United.

On 16 May 2012, Oxlade-Chamberlain was called up to the 23-man senior England squad for UEFA Euro 2012, to be held in Poland and Ukraine. He made his debut for the senior England team on 26 May 2012 in a 1–0 win against Norway in a warm-up match, coming on as a substitute for Ashley Young in the second half. He made his first senior start for England on 2 June playing 66 minutes before being replaced by Theo Walcott in a 1–0 win against Belgium at Wembley Stadium, another warm-up match, and England’s final match before the tournament. On 11 June, he made his major international tournament debut when he started in England’s opening match of the Euro 2012 tournament against France.

On 12 October 2012, Oxlade-Chamberlain scored his first senior international goal, in a 5–0 victory over San Marino. He scored again in the return match against San Marino on 22 March 2013, which England won 8–0.

On 2 June 2013, he scored against Brazil in the official opening of the refurbished Maracanã Stadium, with the match finishing 2–2. He came on as a second-half substitute and scored on a half-volley to bring the score to 1–1.

Oxlade-Chamberlain began the season by winning the 2014 FA Community Shield with Arsenal beating Manchester City 3–0 at Wembley Stadium. On 27 September, he scored in the North London derby in a 1–1 draw against Tottenham. On 4 November, he scored to put Arsenal 3–0 up against RSC Anderlecht in the UEFA Champions League, although the match eventually finished 3–3. He also scored in the round of 16 match against Monaco in February. Two matches later, he was injured in a 2–1 win against Manchester United in the FA Cup and had to be withdrawn just after half-time. It was later confirmed that he would be out for three to four weeks due to the hamstring injury. On 30 May 2015, Oxlade-Chamberlain came on as a substitute in the 2015 FA Cup Final and set up Olivier Giroud to make it 4–0; the final score against Aston Villa at Wembley Stadium.

On 2 August 2015, Oxlade-Chamberlain scored the only goal in a 1–0 victory over Chelsea in the Community Shield. His only league goal that season came away to Bournemouth, the first goal he scored for Arsenal in a league match away from home.

On 23 February 2016, he suffered a serious knee injury in a 2–0 home defeat by Barcelona in the Champions League, which was initially expected to prevent him playing for up to eight weeks. A further injury in May during training prevented his return for the rest of the season, including the summer UEFA Euro 2016 tournament.

In February 2017, Oxlade-Chamberlain was confirmed to be dating singer Perrie Edwards of the girl group Little Mix.

On 31 August 2017, Oxlade-Chamberlain signed a five-year contract with Arsenal’s Premier League rivals Liverpool for a £35 million fee. On 9 September 2017, Oxlade-Chamberlain made his debut for Liverpool, coming on as a substitute in a 5–0 loss to Manchester City. He scored his first goal for the club on 17 October, coming off the bench to score in a 7–0 Champions League win over Maribor, a result which was the joint-largest ever away win in the competition, and the largest away win by an English club. On 4 November 2017, he scored his first league goal for Liverpool in a 4–1 victory over West Ham. On 14 January 2018, he scored the first goal in his side’s 4–3 victory over Manchester City, ending their unbeaten run in the Premier League that season.

On 25 April 2018, Oxlade-Chamberlain suffered a serious injury to his knee in the 15th minute of the Champions League semi-final first leg 5–2 victory against Roma, which prevented him playing further during the season, or participating in the World Cup finals.

On 16 May 2018, due to injury he was left out of Gareth Southgate’s 23-man England national team squad for the 2018 FIFA World Cup.

On 28 December, Klopp stated that Oxlade-Chamberlain’s rehabilitation was going “ahead of schedule” and that “if he makes further steps like he did in the last few weeks then he can play Premier League football this season, which is nice to know”. On 26 April 2019, 366 days after his injury, Oxlade-Chamberlain made his return as a substitute in Liverpool’s 5–0 league win over Huddersfield. He was an unused substitute for the 2019 UEFA Champions League final against Tottenham Hotspur.