Pazienza was born in San Severo in the province of Foggia, and grew up in Foggia Calcio's youth team. He made his debut with the first team in Serie C2 in 2000. Pazienza played with Foggia until 2003, scoring 6 goals in 88 appearances, and helping the team reach the promotion play-offs in 2002, and promotion to Serie C1 in 2003.
He left on loan to Fiorentina for the 2005–06 and 2006–07 seasons for a loan fee of €350,000 annually and was then purchased outright by the club in June 2007 for an additional fee of €3.15 million ; he made 52 league appearances for la Viola in total. During the 2008 winter transfer window, he was purchased by Napoli in a 3½ year contract for a transfer fee of €4.25 million. In total, he made 106 appearances for the club, scoring 4 goals.
On 9 June 2011 Pazienza signed a 3-year contract with Juventus on a free transfer. After only making 8 appearances under Antonio Conte, he moved on loan from Juventus back to Udinese on 31 January 2012, where he played the remainder of the season, making 15 appearances and scoring a goal, for a total of 23 Serie A appearances that season.
On 30 August 2012 he was purchased by Bologna for €300,000 in a 3-year contract, worth €1,081,615 in the first season and €1,261,569 in the second and the third season respectively in gross. The transfer also cost Bologna an additional €366,000 as other fee. Pazienza was ranked joint-4th as the highest earner of Bologna player in 2012–13 season. Pazienza made 37 league appearances for Bologna in the first 2 seasons. However, he did not play any game in his last year of contract in 2014–15 season, which the club was relegated to Serie B.
On 14 July 2015 Pazienza was signed by Serie B club Vicenza Calcio on a free transfer; he was awarded the number 4 shirt. On 4 February 2016, he was transferred to Lega Pro side Reggiana in a 5-month contract. In summer 2016, along with other free agents, Pazienza obtained the license to be a youth team coach.
Although Pazienza primarily excelled as a ball winner, and at breaking down opposition attacks, he was also capable of aiding his team offensively, due to his stamina, work-rate, dynamism, finesse, and ability to make attacking runs into the area; he was also able to aid his team creatively and was an effective assist provider.
