Messi started the season by lifting the Spanish Supercup with Barcelona, scoring three goals and providing two assists in a 5–4 aggregate win against Real Madrid. His vital interventions continued in the next official match played against Porto when he scored again following a weak back pass from Fredy Guarín before setting up Cesc Fàbregas to give Barcelona a 2–0 victory and the UEFA Super Cup, then the only official competition that remained for him to score in.
After scoring his first goal of an eventual hat-trick in an 8–0 rout against CA Osasuna, Messi produced a special celebration for Soufian, a 10-year-old Moroccan boy with Laurin Sandrow syndrome, a rare medical condition that can eventually lead to the loss of the lower extremities. Whilst Messi usually points to the sky after scoring a goal, Messi slapped his thighs as a dedication to Soufian.
In August, Messi became the second highest goalscorer surpassing László Kubala on 194 goals, being behind only to César Rodríguez on 232 goals in all official competitions.
On 28 September, Messi scored his first two Champions League goals of the season against BATE Borisov, becoming Barcelona's second highest goalscorer in its history, tying László Kubala, at 194 goals in all official competitions. He surpassed that record when he scored two goals against Racing Santander. He became second in Barcelona's La Liga goalscorers list with 132 goals, one more than Kubala. He scored his 200th Barcelona goal and two more as part of a hat-trick in his next game against Viktoria Plzeň in the Champions League.
Messi scored a brace in the Club World Cup Final against Santos FC and was recognized as the man of the match and also awarded the Golden Ball for his performance during the tournament.
Messi won the 2011 UEFA Best Player in Europe Award, beating his FC Barcelona team-mate Xavi Hernández and Real Madrid's Cristiano Ronaldo. Messi won the 2011 FIFA Ballon d'Or, again beating his team-mate Xavi and Cristiano Ronaldo. By winning the FIFA Ballon d'Or again, Messi become the fourth player to win three Ballon d'Ors, after Johan Cruyff, Michel Platini and Marco Van Basten and the second player to win three consecutive Ballon d'Ors, after Michel Platini (although two of his Ballon d'Ors are FIFA Ballon d'Ors, which he won consecutively).
On 19 February 2012, Messi, on his 200th La Liga appearance, scored four goals against Valencia CF in a 5–1 win. On 7 March, Messi became the first player to score five goals in an UEFA Champions League match since the tournament's re-establishment in 1992, helping the defending champions Barcelona win 7–1 against Bayer Leverkusen.
On 20 March, Messi scored three goals against Granada CF, making him FC Barcelona's leading goalscorer in official competitions, surpassing club legend César Rodríguez, who had previously held the record with 232.
On 3 April, Messi scored two goals from penalty kicks against Milan in the second leg of the Champions League Quarter-final, allowing him to surpass his personal record, joint with Ruud van Nistelrooy, of 12 goals in a single UEFA Champions League season. These goals allowed him to tie José Altafini's record of 14 goals in a single European Cup season in the 1962–63 season, before the tournament's re-establishment as the UEFA Champions League in 1992. Barcelona were knocked out in the semi-finals to eventual winners Chelsea.
On 11 April, Messi scored his 61th goal against Getafe CF, surpassing Isidro Langara's record of 60 goals in 1933–34, and became the best goalscorer in history in one season in Spain.
On 2 May, Messi scored a hat-trick against Málaga CF surpassing Gerd Müller's record (67 goals in 1972-73) with 68 goals, and thus becoming the best goalscorer in history in one season in Europe. It was the 21st multi-goal game of the season for Messi and his seventh La Liga hat-trick. He then scored four goals on 5 May against RCD Espanyol to take his tally to an unprecedented 72 goals, in the process becoming only the second player to pass 70 goals in a first division season since Archie Stark of Bethlehem Steel in the American Soccer League in 1924–25.
On 25 May, he scored again in the 2012 Copa del Rey Final, helping Barcelona win their 26th Spanish Cup title, and increasing his seasonal goalscoring record to an unmatched 73 goals in all competitions. This was also Guardiola's last match as Barcelona's manager, and the Cup win marked Messi's second Copa del Rey title, after losing the final the year before, as well as his 14th Barcelona trophy during Guardiola's four seasons at the club. Although Barcelona failed to win their 4th consecutive Liga title under Guardiola, finishing runners up to arch-rivals Real Madrid, Messi finished the 2011–12 season as the top goalscorer in La Liga for a second time, with a Liga record of 50 goals. He was the second best assist provider in La Liga that season with 16 assists, after Mesut Özil, who managed 17. He also ended the season as the UEFA Champions' League Top Scorer for a fourth consecutive time, with 14 goals. He was one of the top assist providers of the tournament with 5 assists and finished the season with 73 goals and 29 assists in all club competitions, with more goals and assists than any other player.