Iaquinta was born in Cutro, in the province of Crotone. Like many Calabrians in the 1980s, his parents migrated to Emilia-Romagna in Northern Italy for better job opportunities. Iaquinta played with his brother in the lower divisions for Reggiolo for the 1996–1997 season, before transferring to Serie B club Calcio Padova in January 1998, after 33 appearances and 6 goals in his first professional season and a half.

Iaquinta moved to Padova in January 1998, a club where his future Juventus teammate and Italian legend Alessandro Del Piero thrived, but his spell with Padova was short-lived as after only 6 months, just 13 appearances and 3 goals, Iaquinta was surprisingly sold to Serie C1 club, Castel di Sangro Calcio.

In June 2000, Udinese completed the signing of the young prospect and in his first season with the club, Iaquinta made 16 appearances and scored 2 goals. The following season, he made 26 appearances with 3 goals, before breaking into the starting eleven in his third season. He scored 8 goals in 28 appearances and the following season (2002–03), in which Udinese finished in 6th and qualified for the UEFA Cup. Iaquinta made 32 appearances and scored 11 goals during the 2003–2004 season, as his team again reached the UEFA Cup, this time in 7th.

Iaquinta has been married to Arianna Cucinotta since 14 June 2003. He and his wife have four children, two sons and two daughters: Giuseppe, born on 17 December 2002, Edoardo, born on 28 June 2004, Carlotta, born on 20 May 2008, and Ginevra, born on 23 April 2015.

Iaquinta made his international debut for Italy on 30 March 2005, as a half-time substitute for Luca Toni in a 0–0 home friendly draw against Iceland at the Stadio Euganeo in Padua.

Juventus signed Iaquinta on a five-year contract on 19 June 2007 for a fee of €11.3 million. (cash plus Michele Paolucci), to become the Turin giant’s first signing for the new campaign. Udinese also bought back Fabio Quagliarella from Sampdoria on 21 June; Sampdoria then bought Andrea Caracciolo from Palermo on 22 June and Palermo bought Fabrizio Miccoli from Juventus on 5 July.

During the 2007–08 season, Iaquinta made only a handful of starts for Juventus, mostly being used as back-up to the experienced strike partners Alessandro Del Piero and David Trezeguet, who combined to score 41 goals between them in the Serie A alone. He did however still manage 29 appearances with 9 often crucial goals, such as his last minute winner versus Napoli in April 2008. It appeared that he might be surplus to requirements after the signing of Brazilian striker Amauri, leading to rumours about a possible move out of Juventus. However, nothing materialised, and Iaquinta remained for the 2008–09 season. Iaquinta also signed a new 4-year contract near the end of 2008–09 season.

Iaquinta was a member of the Italian squad that won the 2006 FIFA World Cup under manager Marcello Lippi. His first international goal came in his nation’s opening match of the tournament, on 12 June: Iaquinta scored Italy’s second goal in the 2–0 victory against Ghana. He played in 5 out of 7 of Italy’s matches, including the victorious semi-final against hosts Germany and final against France on 9 July, in which he came on after 61 minutes for Simone Perrotta. Iaquinta missed out on Roberto Donadoni’s Italy squad for Euro 2008 due to injury. He later took part at the 2009 FIFA Confederations Cup, and he also played for Italy in the 2010 FIFA World Cup, in which he scored a penalty in a 1–1 draw against New Zealand in the second group match. His 40th and final international appearance came in the last group game on 24 June, in which Italy were defeated 3–2 by Slovakia and eliminated from the tournament. In total he scored six goals for Italy.

Under new coach Antonio Conte in 2011, Iaquinta, Amauri and Luca Toni did not play a single minute on the pitch and Iaquinta was the third one to leave Turin on 31 January.

On 31 January 2012, Iaquinta joined Cesena on loan until the end of the 2011–12 season. He made his debut for them on 9 February away at Lazio, and assisted Adrian Mutu for the first goal and scored a penalty to put Cesena 2–0 up at half-time, but they eventually lost 3–2. In total he made 7 appearances for the club, although his time with Cesena was once again characterised by injuries, and he was unable to save the club from relegation.

At the end of the season he returned to his home club Juventus, who had just won the league title, although he continued to struggle with injuries, and once again failed to make a single appearance under Conte during the 2012–13 Serie A season, as Juventus won a second consecutive league title. On 22 July 2013, following the end of his contract with the club, he announced his retirement, stating his intention to pursue a coaching career.

During the Aemilia antimafia investigation, on 4 February 2015 illegal weapons were found at Iaquinta’s Quattro Castella home and his father Giuseppe’s home. On 21 December 2015, they were both sent to trial for the illegal possession of firearms, aggravated by the aiding of the Calabrian Mafia organization ‘Ndrangheta expand to Northern Italy, of which his father was charged with association with the ‘Ndrangheta through the ‘Ndrina of Nicolino Grande Aracri. On 31 October 2018, Iaquinta was found guilty of illegal possession of firearms, and sentenced to two years imprisonment; his father was found guilty of mafia association, and received 19 years imprisonment.