Iniesta spent most of his career at Barcelona, where he played a major role in the club's success along with his midfield partners Xavi and Sergio Busquets.

Iniesta was an integral part of the Barcelona sides that won two historic trebles in 2009 and 2015, and his 35 trophies, which include nine La Ligas and four UEFA Champions League titles, make him the most decorated Spanish footballer of all time.

At UEFA Euro 2012, Iniesta led Spain to their second consecutive continental crown, again being chosen as the Man of the Match of the final against Italy, and was named the Player of the Tournament.

[13] He captained the Barcelona Under-15 team to victory in the Nike Premier Cup of 1999, scoring the winning goal in the last minute of the final, and was named player of the tournament.

[22] Don Balón, a member of European Sports Magazines, named Iniesta one of the most consistent performers in the previous two seasons of La Liga; he placed fifth in 2006–07 and fourth in 2007–08.

[25] At the start of the 2008–09 season, in September 2008, Iniesta was elected the fourth-choice captain behind, in order of preference, Carles Puyol, Xavi and Víctor Valdés; all four were products of the Barcelona youth system.

[27] A leg injury sustained in mid-November 2008 left Iniesta sidelined until 3 January; initially expected to return to action in six weeks, he did not want to come back until he was 100 percent.

Upon his return to action on 3 January, as a 65th-minute substitute against Mallorca, he scored a crucial goal after just ten minutes on the pitch and completed a Barcelona comeback in front of the Camp Nou.

[28] 3 days later, he captained Barcelona for the first time in an official match, a 3–1 victory against Atlético Madrid at the Vicente Calderón in the round-of-16 first leg of the Copa del Rey.

Iniesta sustained another injury during a home match against Málaga, but returned to action for the first leg Champions League quarter-final against Bayern Munich on 8 April, which Barcelona won 4–0.

"[12] Despite a thigh injury, Iniesta played and was influential in the game, providing the assist for the first goal scored by Samuel Eto'o as his team went on to win 2–0.

[33] In his analysis, David Pleat wrote, "In the end the midfield artistry of Iniesta and Xavi, helped by [Lionel] Messi, was the critical factor.

[42] A contributing factor of Iniesta's fractured season were the episodes of psychological instability he suffered privately following the death of his close friend Daniel Jarque, a fellow footballer, in August 2009.

"[45] Iniesta scored his first goal of the 2010–11 season during the opening league fixture against Racing de Santander, lobbing the ball into the net from a distance of 30 yards.

[46] Throughout the campaign, he received standing ovations from opposition fans, including at El Sardinero and the Vicente Calderón Stadium, in appreciation of his World Cup-winning goal.

[56] During the first Clásico of the 2015–16 season, on 21 November, Iniesta became only the third Barcelona player, after Diego Maradona in 1983 and Ronaldinho in 2005, to receive applause from Real Madrid fans at the Santiago Bernabéu.

[68] On 7 December 2020, Iniesta suffered a tear of the rectus femoris muscle during a 2–0 win in the round of 16 of the 2020 AFC Champions League against Shanghai SIPG, in which he also scored the first goal of the game.

[79] He made his debut on 19 August 2023 against Al Wasl, coming off the bench in the second half, in a match ended with a 0–1 defeat as the Emirates failed to create a single shot on target.

He played in the first two of Spain's group stage matches and proved an important part of the team, providing a pass for David Villa's second goal against Russia.

In the semi-final against Russia, he played the entire 90 minutes and produced a cross that Xavi converted to open the scoring in an eventual 3–0 victory;[88] he was subsequently named the Man of the Match.

Iniesta did not participate in the 2009 FIFA Confederations Cup in South Africa due to a thigh muscle injury; Spain was eliminated from the tournament at the semi-final stage.

[93] He earned a yellow card for removing his jersey during his ecstatic goal celebration to reveal his message to his late friend Dani Jarque.

[98] At the 2013 FIFA Confederations Cup, Iniesta was named in the Team of the Tournament and awarded the Silver Ball for the second best player in the competition, as Spain finished runner-up to host nation Brazil.

"[12] He was used initially as a wide-forward in the absence of Juan Román Riquelme and Ronaldinho by Louis van Gaal and Rijkaard respectively, but made his name as a world-class player in central midfield alongside or in lieu of Xavi, at both club and international level.

A diminutive midfielder, Iniesta was a player known for his passing, technique, vision and movement;[12][109][110] he was also highly regarded for his ability to read the game, as well as his acceleration, and close control at speed, which — when combined with his low centre of gravity — rendered him one of the most skilled dribblers of all time,[111] by allowing him to change direction quickly, get past opponents, and undertake individual runs with the ball, despite not being particularly quick.

Moreover, Iniesta's former manager Guardiola praised him for "his mastery of the relationship between space and time", which he utilises to his advantage in order to disorient opposing players when in possession.

Much like other Barcelona youth products such as Pep Guardiola, Xavi and Iván de la Peña, Iniesta was a playmaker who relied on his technique, passing, intuition, movement and inventiveness to control the midfield, dictate the ebb and flow of play, and create chances or space for teammates.

[12][120][121] Iniesta was praised for his understanding and interplay with Xavi; former Barcelona teammate Giovanni van Bronckhorst said of the pair, "They have a special relationship, they always have, they just seem to know where the other one is.

[146] In May 2018, Iniesta revealed to Risto Mejide that he suffered from depression before the 2010 FIFA World Cup due to his injuries and the death of Daniel Jarque.

[147][148] In September 2018, Iniesta alongside German footballer (and Vissel Kobe team-mate) Lukas Podolski campaigned and donated money for the victims of the Hokkaido Eastern Iburi earthquake in Japan.