A northern classics specialist, Pozzato has finished 13th (2006), 14th (2007), 6th (2008), 2nd (2012) and 8th (2017) at the Tour of Flanders. His best finish at the Paris–Roubaix was 2nd in 2009. (He also delivered a respectable 15th in 2006). At the Gent–Wevelgem Pozzato finished 13th (2008) and 4th (2006). In the Omloop Het Volk he finished 6th (2003) and 1st (2007). Pozzato also won the 2006 Milan–San Remo, and has won stages in all three Grand Tours.
Born in Sandrigo, Veneto, Pozzato turned professional in 2000 with the Mapei–Quick-Step cycling team, part of the famous classe di '81 a group of emerging young riders born in 1981 who were part of the Mapei TT3 development team. Other alumni include Fabian Cancellara and Bernhard Eisel, Alexandr Kolobnev and Gryschenko.
After Mapei ended its sponsorship in 2002 Pozzato joined Giancarlo Ferretti's Fassa Bortolo cycling team. Despite his win of Tirreno–Adriatico in 2003 and a stage win in the 2004 Tour de France, personality clashes with Ferretti meant that Pozzato suffered poor years with Fassa Bortolo in 2002–2004. During this period he was injured for some time and had to work for star sprinter Alessandro Petacchi at other times.
During the 2004 season he was chosen to be part of the Italian 2004 Olympics team in support of team leader Paolo Bettini who went on to win the event.
He re-established contact with several managers and directeurs sportif of Quick-Step–Innergetic. The Quick Step-Innergetic team expressed interest and Pozzato was able to obtain a release for the 2005 ProTour season, joining several former Mapei riders already on the team, such as Paolo Bettini and Davide Bramati.
The 2005 ProTour season went better for Pozzato, with a win in the HEW Cyclassics in front of teammate Luca Paolini.
The 2006 season saw him win the first major classic of the year Milan–San Remo after a superb ride which saw him first work for team leader Tom Boonen, but then was forced to launch his own winning attack in the finale.
For the 2007 season, Pozzato joined the Liquigas squad, and began his season in style, winning the Tour du Haut Var the Omloop Het Volk and Stage 5 of the Tour de France.
In 2009 he won the E3 Prijs Vlaanderen. His results show experience, comfort, and power on the cobblestones and on the Belgian hills ("hellingen"). In aftermath of his 2nd place in the 2009 Paris–Roubaix, Pozzato claimed that when avoiding a crash of Thor Hushovd he lost 4 or 5 seconds and the chance for victory. He also suggested that Boonen benefited from the slipstream of official motorcycles to augment his lead.
In 2010 he has been accused by several riders, including Bjorn Leukemans, Boonen and Philippe Gilbert for his "negative tactics" during key races. This resulted in the nickname "The Shadow".
In 2013, Pozzato earned his first victory of the year in the Trofeo Laigueglia, held in Liguria, Italy on mainly narrow, twisting and turning roads. His team Lampre–Merida reeled in the breakaway and controlled the front of the leading group when Mauro Santambrogio (Vini Fantini–Selle Italia) attacked with 3 kilometres (1.9 mi) to cover, with Pozzato jumping in his slipstream. The sprint was contested by 4 riders, Pozzato getting the best of them. This marked Pozzato's third win in the event, a record in the race's history. In September, he raced the GP Ouest-France and despite not being a top favourite, he won the race, becoming just the fifth Italian to do that.
In 2016 Pozzato will be racing for a new team, the Italian-based Southeast Pro Cycling Team.
In 2012, Pozzato was banned from cycling for three months by the Italian National Olympic Committee (CONI) after it was found that he had worked with infamous doctor Michele Ferrari from 2005 to 2008. CONI had looked to ban him for a year but were forced to reduce it to a three months thanks to a technicality.
In May 2016 during the 2016 Giro d'Italia, Pozzato disclosed via his Twitter account that he was 'coming out'. Although he did not specify that he was coming out as gay, the tweet included an image of Pozzato in bed with another man.