Liuzzi was born in Locorotondo, Bari, in the Apulia region of southern Italy. He began kart racing at the age of nine, winning the Italian Karting Championship in 1993 and placing second in the Karting World Championship in 1995. He secured the World Karting Championship in 2001, a title made notable by his victory over Formula One champion Michael Schumacher at Kerpen, Schumacher's home track.
After karting, Liuzzi moved into single-seaters, finishing second in the 2001 German Formula Renault Championship. In 2002 he joined the Red Bull Junior Team for the German Formula Three Championship, finishing ninth and recording a victory at the Imola International F3 race. He also conducted test drives for Coloni and Williams that year.
Liuzzi spent the 2003 F3000 season with Red Bull, finishing fourth, before moving to Arden for 2004. His 2004 campaign was dominant: he won seven of the ten races and wrapped up the International Formula 3000 title with one round remaining.
Liuzzi's F3000 form prompted Ferrari test interest, and he tested with Sauber in September 2004 before Red Bull hired him for 2005. Christian Klien was given the race seat alongside David Coulthard, but Red Bull had previously agreed that both Liuzzi and Klien would race during the season. Liuzzi replaced Klien for the San Marino, Spanish, and Monaco Grands Prix, scoring his maiden championship point on debut in San Marino after both BAR drivers were disqualified. He received one additional start at the European Grand Prix before Klien's seat was restored.
Following Red Bull's purchase and renaming of Minardi as Scuderia Toro Rosso, Liuzzi was awarded a full race seat for 2006. He scored the team's first-ever championship point with an eighth-place finish at the United States Grand Prix, produced after a sustained battle with Coulthard and Nico Rosberg.
Retained for 2007, Liuzzi faced constant speculation about his future as the team evaluated Sebastian Vettel and Sebastien Bourdais. Once Bourdais was confirmed for 2008, Liuzzi's performances improved significantly. At the 2007 Chinese Grand Prix he qualified eleventh, gained places at the start, overtook Mark Webber and Nick Heidfeld during the race, and finished sixth — considered among the best drives of his Formula One career.
After Toro Rosso confirmed Bourdais for 2008, Liuzzi joined Force India as test driver. In September 2009, when Giancarlo Fisichella was released to replace Luca Badoer at Ferrari following Felipe Massa's injury, Liuzzi stepped up to a race seat for the final five rounds of the 2009 season. At the Italian Grand Prix he qualified an impressive seventh despite carrying a heavier fuel load than his teammate Adrian Sutil.
Retained for a full 2010 campaign alongside Sutil, Liuzzi achieved a career revival. He scored points in Bahrain, Australia, Monaco, Canada, Belgium, and Korea, matching his best finish of sixth at the Korean Grand Prix. He ended the season fifteenth in the championship with 21 points — his best career total — before Force India replaced him with Paul di Resta for 2011, despite his holding a valid contract.
Liuzzi joined Hispania Racing for 2011 alongside Narain Karthikeyan. He did not qualify for the Australian Grand Prix and retired in Malaysia after the team withdrew him for safety reasons. He recorded his first finishes for the team in China and Turkey, took a sixteenth place in Monaco and thirteenth in Canada — Hispania's best result at that point — and continued to finish at the back of the field throughout the year. He was temporarily replaced by Karthikeyan for the Indian Grand Prix, but returned for Abu Dhabi and the finale in Brazil, where he retired from a points-unlikely but competitive position after an alternator failure on lap 61. His contract for 2012 was ultimately not honoured when Karthikeyan was handed the seat.
In 2012, without a Formula One drive, Liuzzi joined the International Superstars Series with CAAL Racing in a Mercedes C63 AMG, taking his first podium at the opening round at Monza and adding a race win later in the season. In 2014, he moved to Japan and competed in both Super GT (GT500 class) with Autobacs Racing Team Aguri alongside Kosuke Matsuura, and in Super Formula.
In 2013, Liuzzi and Johnny Herbert mentored six contestants on a primetime ITV4 reality series in which Gran Turismo players competed for the chance to race at the Dubai 24 Hour race as real drivers.
Liuzzi speaks Italian, English, and French. He is married to Francesca Caldarelli, making him a brother-in-law of racing driver Andrea Caldarelli.
Liuzzi represented a generation of talented Italian drivers who reached Formula One via the Red Bull programme and spent their careers proving consistent pace without ever landing the equipment needed to challenge regularly for points. His 2007 Chinese Grand Prix performance and his 2010 Force India campaign — in which he out-qualified and occasionally outperformed teammates with more institutional support — remain the clearest indicators of his ability at the top level.