He played for the Paraguay national team from 2000 to 2017, and is their most-capped player of all time, earning over 100 caps. He played at two World Cups and three Copa América tournaments, helping his country finish as runners-up in the 2011 Copa América.
Born in Asunción, Da Silva started his career in the youth divisions of Atlántida Sport Club, arriving at the club at the age of 13. In 1996, da Silva reached the Primera División Paraguaya with Asunción team Presidente Hayes at the age of 16.
Before joining Toluca, da Silva played for Perugia and Venezia of Italy, and Lanús of Argentina. He joined Toluca from Paraguayan Club Libertad for the 2003 Apertura. After making his debut, da Silva was a mainstay in Toluca's defence, starting all but one game that he has played and eventually becoming the team's captain due to his leadership on the field. In 2007, he was chosen for the "Ideal Eleven" squad of South America and in 2008 he led Toluca to the Apertura 2008 title, being chosen as the best overall player of the tournament by the Mexican media.
On 13 July 2009, Da Silva joined English club Sunderland on a three-year deal. Manager Steve Bruce said "I'm delighted to have signed a player of Paulo's experience. He is captain of his country and has played at the highest level in South America, so will bring leadership qualities to our side." His arrival at the Stadium of Light was followed by a long and confusing period in regards to his visa application. Da Silva was granted a work permit to play in England almost immediately, but had to wait for over a month to get his visa before it was eventually granted on 12 August.
He made his debut on 24 August against Norwich City in the League Cup second round, playing the whole 90 minutes of a 4–1 away win. On 12 September he made his first Premier League appearance, replacing Steed Malbranque for the final ten minutes of a 4–1 home win over Hull City.