Paletta starred for the Argentinian under-20 team, that won the 2005 FIFA World Youth Championship, alongside starlets such as Lionel Messi and Sergio Aguero. He had come a long way in one year, having established himself at Banfield, a small club in the greater Buenos Aires. Liverpool's scouts were impressed by the towering centre-half and wasted no time signing him. BBC'S South American expert, Tim Vickery, was impressed by the highly-promising defender, but felt at the time Paletta needed "some more mileage before making the move across the Atlantic." He also said: "Paletta is one of those complicated South American cases of a player whose registration is not wholly owned by a club. There are other investors involved, who typically prefer short-term profit to long term career development. Instead he has skipped a stage. Finance has won over football." Vickery proved to be right to assume that Paletta would struggle. He played eight times in Liverpool's first team in his only season at Anfield, mainly in the League Cup but also in the Premier League towards the end of the season when Rafa Benítez had one eye on the upcoming Champions League final when it came to team selection. The young Argentinian clearly had difficulty in adapting to English football, which was painfully clear during Liverpool's 6-3 loss to Arsenal at Anfield in the fifth round of the League Cup.

Paletta joined Boca Juniors at the start of the 2007/08 season. He helped Boca reach the semi-final of the 2008 Copa Libertadores, where the Buenos Aires club lost 5-3 on aggregate to the Brazilians from Fluminense. In July 2010 Paletta left for Italian Serie A club Parma. The Argentinian was clearly more ready now than four years earlier to leave his homeland. He has become a firm fixture in the middle of Parma's defence, making over 100 appearances in three years. Paletta was so impressive that the Italian national team utilised the fact that his great-grandfather, Vicenzo, was born in Crotone, Calabria before he emigrated to Argentina. Paletta made his international debut for Italy in a 1-1 friendly against Spain on 5 March 2014 and played against England in the World Cup in Brazil.

The Argentinian defender played in Serie A 21 times for Parma in the 2013/14 season and added two more appearances in the Coppa Italia. Parma's 6th place finish in the league ought to have seen them qualify for the Europa League Third Qualifying Round. But that place went instead of 7th placed Torino because UEFA refused to give Parma a licence because of an overdue tax debt. With Parma imploding financially, he was sold to AC Milan at the end of the January 2015 transfer window and then loaned to Atalanta for 2015/16, where he played 24 times scoring once.

For 2016/17 Paletta was back with AC Milan and a regular in central defence. However, in 2017/18 he was out of favour and played just once, in the Europea League, before moving to Chinese Super League side JS Suning in January 2018. He played 24 times in the league for them in the 2018 season, scoring once and remained there for a second year in 2019. In November that year he joined Italian Serie C side Monza, who were declared champions of their section after the season was cut short due to Covid 19. Paletta remained with them at the start of 2020/21, their first campaign in Serie B for twenty years. In 2021/22 Monza were promoted to Serie A but a hamstring injury meant he failed to make an appearance in Italy's top flight. Paletta's contract was terminated by mutual consent in February 2023 and he retired from playing.