Ganso was brought to Tuna Luso after being discovered by former Brazil international Giovanni, and at 15 years of age he joined Paysandu, but he was snapped up by Santos in 2005.

In 2007, after an injury that sidelined him for six months, Ganso played in and won the final of the U-20 Campeonato Paulista. He wore the number 10 jersey in Santos’ campaign in the Copa São Paulo of 2008, where his team was eliminated in the quarter-finals by Sport Club Internacional. He won the 2010 Campeonato Paulista with Santos on 2 May 2010, defeating Santo André in the final.

In 2009, he was called up to play for Brazil in the World Under-20 Championships. In early 2010, the Brazilian media began calling for Brazilian national team coach Dunga to choose Ganso for the 2010 World Cup in South Africa, primarily as a substitute for Kaká, because of their similar styles of play. On 11 May 2010, he was named as one of seven backup players for the 23-man 2010 FIFA World Cup Brazil squad. On 26 July 2010, he was called up by the new coach Mano Menezes to the “Seleção” for a friendly match against USA. On 10 August 2010, in a friendly against the USA he made his senior debut, where one of his shots rattled the post, almost giving him his first senior international goal. He was named in Mano Menezes 23-man 2011 Copa América squad and was given the number 10 shirt. During their second group game against Paraguay, on 9 July, Ganso assisted Jádson’s goal as well as a last minute equalising goal from Fred to tie the game at 2–2. Brazil were later eliminated by Paraguay in the quarter-finals of the tournament, following a penalty shoot-out.

In August 2010, it was reported that Ganso would have surgery on his injured left knee and would be out for six months.

Ganso has been a fundamental presence in midfield for both Santos and São Paulo, due to the enormous quality of his passes. After being a potential favorite name to wear the number 10 shirt for Brazil in the 2010 FIFA World Cup, Ganso was not called up for the tournament by Dunga, the nation’s national football coach at the time, as the number 10 shirt went to Kaká. After suffering recurring injuries and a decrease in form and match fitness, he subsequently lost his place in the Brazilian team, in favour of Oscar, due to his performances with his club at the time, Chelsea. In 2012, Ganso refound his form and put on a notable performance in the derby against Corinthians, helping his team to a 3–1 victory, and, in 2013, he shone in a 2–0 win against Atlético Mineiro, as São Paulo advanced to the third stage of the 2013 Copa Libertadores.

On 20 September 2012, after a hard period of negotiation, it was confirmed by São Paulo that Ganso had signed a five-year contract, for a R$23.940 million transfer fee. Ganso would wear the number 8, previously used by Fabrício.

Ganso took part in the 2012 Summer Olympics in London, where Brazil achieved a silver medal.

After getting back in great shape, Ganso was praised by his coach in São Paulo, Muricy Ramalho. According to Ramalho, who worked with Ganso in Santos, when both of them won 2011 Copa Libertadores, and in October 2013, when his number 8 shirt passed Jádson as the main assistant of Tricolor in the 2013 season: “Now, we have a number 10 shirt.” In Brazil, this number is associated with playmaking.

After Muricy Ramalho’s arrival, Ganso had put on good performances. On 16 October 2013, he scored a notable goal in São Paulo’s 3–0 victory over Náutico in the Brazilian League, dribbling past four opponents before shooting on goal past the keeper.

Ganso started 2014 in a bad phase, but after Jádson left in a negotiation that brought Alexandre Pato to São Paulo FC he was awarded the number 10 shirt, and was hopeful that the new jersey number would give him confidence, and that his performances would improve. Ganso stated: “I am very happy to wear the shirt of São Paulo and, now, to be given the number 10 shirt. This number was already worn by so many good players and I feel an immense happiness to be among them. My playing style is more traditional and I am told that a number 10 must know how to play in this manner. I think I will be able to combine the efficient with the aesthetic: classic football with the number 10 shirt.”

On 16 July 2016, Ganso signed to La Liga Spanish side Sevilla FC for a fee of €10 million. He scored his first league goals for the club on 21 April 2017, netting a brace in a 2–0 win over Granada.

On 31 August 2018, the last day of the 2018 summer transfer window, Ganso joined Ligue 1 club Amiens SC on a season-long loan. Amiens secured an option to sign him permanently.

On 31 January 2019, Ganso returned to Brazil and signed a five-year contract with Fluminense.