On 1 January 2011, van Persie scored his first goal of the season in a 3–0 away win over Birmingham City. On 15 January, he added two more goals to his tally in a comfortable 3–0 win over West Ham. This made him only the fourth Dutchman to reach 50 goals in England's top division. Van Persie scored his first career hat-trick in a 3–0 win over Wigan Athletic on 22 January and two goals against Newcastle United in a 4–4 draw on 5 February. Continuing his fine form, he hit a brace the following week against Wolverhampton Wanderers scoring both Arsenal goals in a 2–0 win including a volley from inside the box. The ten goals he scored between 1 January and 12 February set a new Premier League record for most goals scored in the first two months of a calendar year.
Van Persie set the Emirates alight with a goal from an almost impossible angle in Arsenal's fightback against Barcelona in the UEFA Champions League Round of 16, which ended 2–1 in favour of the Gunners. On 27 February 2011, Van Persie captained Arsenal at Wembley Stadium in the League Cup final, scoring the first half equalizer for the Gunners. It was his first goal at Wembley and his first in a cup final for Arsenal. However, he was later taken off in the second half with a knee injury he picked up while scoring the goal.
On 1 March 2011, he was ruled out for three weeks, which would see him miss the Champions League return leg with Barcelona. However, he recovered in time for the return leg at Camp Nou. During the game, he received a yellow card in the first half for a foul. In the second half, he was sent off after he received a second yellow card when the referee, Massimo Busacca, deemed him to be time-wasting by taking a shot at goal after the whistle was blown (one second earlier) for offside. Barcelona went on to score twice more and advanced to the quarter finals on a 4–3 aggregate result. Afterwards, Van Persie branded Busacca's decision as a "total joke", claiming that with the noise of the 95,000-strong crowd he could not hear the whistle. On 19 March 2011, he scored the equalizing goal in a 2–2 against West Bromwich Albion at The Hawthorns. The match finished 2–2 with Arsenal still five points behind the current leaders, Manchester United.
On 10 April 2011 in a match against Blackpool, Van Persie put in a Man of the Match performance to give Arsenal a crucial 3–1 win as he set up a goal and scored the third. On 24 April 2011, he became the first player to score in seven successive Premier League away games when he scored against Bolton, beating Didier Drogba's record who was on six successive away games, between August and November 2009. However, the Gunners lost 2–1, all but ending their title hopes. On 1 May he assisted Aaron Ramsey who scored the winning goal against league leaders Manchester United to add a twist to the Premier League. Van Persie was named Premier League Player of the Month for April.
On 8 May 2011, Arsenal lost 3–1 against Stoke City at the Britannia Stadium. Van Persie scored the goal for Arsenal and extended his Premier League record by scoring in an eighth successive away match. In the last home game of the season, he scored against Aston Villa, but Arsenal lost the match 2–1. In the last game of the season away to Fulham, he managed to score in his ninth consecutive away match, bringing his goal tally for the season to a personal record of 18 league goals. He also equalled the record held by Cristiano Ronaldo and Thierry Henry by scoring 18 league goals from the turn of the year to the end of the season. He ended the season just two goals behind joint league top scorers, Carlos Tevez and Dimitar Berbatov in the race for the golden boot, despite being injured for half of the season. He was voted as the second best player of the 2010–11 season on Arsenal's official website and also received the team's Goal of the Season award for his audacious strike in the 2–1 victory over Barcelona in the Champions League.
Having been appointed vice-captain for the 2010–11 season, Van Persie was promoted to club captain following the transfer of Cesc Fàbregas to FC Barcelona at the start of the 2011–12 season. On 24 August, Van Persie scored his first goal of the 2011–12 season in the second leg of Arsenal's 2–1 away victory against Udinese in a Champions League play off match. On 24 September 2011, he scored twice against Bolton Wanderers to raise his tally for Arsenal to 100 goals, becoming the 17th Arsenal player to reach this milestone.
On 16 October 2011, he scored the fastest goal of the 2011–12 Premier League season, 28 seconds into a home match against Sunderland. He went on to score a late winner from a curling left foot free kick, to put Arsenal 2–1 ahead. After the match, Van Persie stated his dedication to the club after speculation surrounding a future transfer away from the Emirates. On 23 October, he came on as a substitute in the 66th minute replacing Marouane Chamakh and scored two goals against Stoke City. The match ended 3–1 with another home win for Arsenal.
He then continued his scoring run for Arsenal on 29 October by scoring a hat-trick in Arsenal's 5–3 victory against Chelsea at Stamford Bridge. Due to his consistent performances and good goal-scoring form, Van Persie was named the Premier League Player of the Month for October 2011. He continued scoring as he scored Arsenal's opening goal of the match in their 3–0 win over West Bromwich Albion on 5 November along with two assists. After the international break, he scored both Arsenal goals against Norwich City to help the Gunners to a 2–1 win on 19 November 2011. In Van Persie's fifth Champions League match of the season he scored twice in the 49th and 86th minute to lift Arsenal to a 2–1 victory over Borussia Dortmund and to qualify Arsenal for the knockout phase on 23 November 2011.
After failing to score against Fulham, Van Persie scored again for Arsenal, this time against Wigan Athletic to make the score 4–0 to Arsenal on 3 December 2011. He then added to his tally with the only goal of the game against Everton, an exquisite volley from an Alex Song long ball. The following match, versus Aston Villa, saw him score a penalty and provide an assist. Van Persie's final goal of the 2011 calendar year came in Arsenal's one-goal win over Queens Park Rangers on the last day of the year. The goal took his tally for the year to 35 goals, one short of Alan Shearer's Premier League record.
On 2 September 2011, Van Persie scored four goals in a record breaking 11–0 victory in UEFA Euro 2012 qualifying Group E over San Marino. He entered the Dutch national team's top 10 all-time topscorer ranking with a tally of 25 goals, dislodging Marco van Basten in the process. Van Persie had not scored four goals in a single match for a long while. Van Persie contributed six goals in total during qualifying.