Barrientos began his professional career in 2003 with San Lorenzo, as he officially was promoted from youth team football to the club's first team. He instantly became a big hit for the Argentine club, and his performance saw him begin to earn call-ups to the Argentine U-20 and U-21 football teams. At the age of 21, the player had already managed 72 league appearances with 7 league goals, also earning 15 caps and scoring 6 goals for his country. The player's impressive form lead to many transfer rumours, and the player was linked to a host of European clubs. However, in July 2006, Barrientos transferred to FC Moscow, of Russia.
Following his move to Russia, the player did not hold down a guaranteed starting spot and after two seasons in the Russian Premier League, the 23-year-old Barrientos made 33 league appearances and scored 6 goals. For the 2008–2009 season, Barrientos was sent back to San Lorenzo, on a long loan deal. Despite not playing the full season at his former club, Barrientos still managed to score a very impressive 9 goals in just 21 league starts. Following his return to Moscow, the player was again linked to several different clubs, after his excellent loan period in Argentina. In May 2009, it was confirmed that Barrientos signed for Sicilian giants, Calcio Catania in the Italian Serie A.
On 30 May 2009 Calcio Catania officially signed the Argentine from FC Moscow on a 4-year contract until June 2013. The player's highly anticipated transfer from was far from successful, as he was constantly plagued by injury and failed to make his debut for the Sicilian club until May 2010. After making just 2 substitute appearances for Catania in the whole of the 2009–10 season, Barrientos did not play any matches in the first half of the 2010–11 Serie A season. Therefore, he was loaned to Estudiantes back in Argentina for 6 months. After a very successful loan spell that saw the player score an impressive 5 goals in 7 league matches, Barrientos returned to Catania in July 2011 and has since become a key component to the team under new head coach, Vincenzo Montella, finally fulfilling the potential seen in him when Catania signed him three years previous for a hefty €4m. During the 2012-13 Serie A campaign, Barrientos has been a key part of Rolando Maran's first team, scoring 5 goals in 27 league appearances. He has formed part of an all-Argentine attack force with Gonzalo Bergessio, Alejandro Gómez, and Lucas Castro for the Sicilian club that has seen i rossazzurri push for the European places.
Barrientos is part of a record-breaking Catania outfit that had picked up 56 points from 38 Serie A matches. This performance saw the club also break its record number of home victories in a single season, its record number of victories overall in a single top flight campaign, as well as its record points total in Serie A for the fifth consecutive season.
As of 2 July 2014, it has been reported that Barrientos will return to San Lorenzo, the team in which he made his debut as a professional player. This will be his third time playing for El Ciclón. The details of the transaction have yet to be released.
On July 29 2016, Barrientos signed for Deportivo Toluca.
After receiving 15 U-21 caps for his country in which he scored 6 goals, Barrientos received a call-up to the Argentina squad against Chile on 15 November 2008 by Alfio Basile.San Lorenzo
Copa Libertadores: 2014
Supercopa Argentina: 2015
Pablo's brother, Hugo is a fellow footballer playing in Argentina.