Matuzalém began his career at Salvador-based Vitória and quickly established his place in lower level of the Brazil national team. Known as a goalscoring midfielder, he first emerged in the 1997 FIFA World Youth Championship in Egypt. There, he scored three goals in six games, including a critical goal in the final match.
In 1999, Matuzalém left Vitória to join Napoli in Italy, via Parma, in a temporary deal, where he remained for two seasons, the first spent in Serie B and the second season in what would be Napoli's last in Serie A for six years. The club signed Matuzalém in co-ownership deal for 5 billion lire in summer 2000. Matuzalém was a regular starter at Napoli, but only scored twice during his tenure in Naples.
Following his Napoli spell, Matuzalém was bought back by Parma, subsequently reselling half of his rights to Piacenza in another co-ownership deal in the summer of 2001, for 6 billion Lire (€3,098,741).) Matuzalém stayed at Piacenza alongside Amauri, Nicola Mora and Matteo Guardalben, all of which were also partly owned by Parma.
With Piacenza at 2001–02 season, the team finished 14th in the league. In the opening round of the season, Matuzalém became the first foreigner to score for Piacenza in the Serie A. In June 2002, Parma reacquired all of his rights again.
The second season of the loan spell saw Matuzalém switch to Brescia on loan, where he played nearly every match and the deal was made permanent at season's end. However, he only lasted one more year, before Ukrainian giants Shakhtar Donetsk signed him.
In June 2004, Shakhtar Donetsk signed Matuzalém from Brescia, paying Brescia €8,000,000, Matuzalém's agents €3,750,000 and €221,092 to Matuzalém's former clubs as solidarity contribution. It was a Ukrainian record at the time. After the transfer of Anatoliy Tymoschuk to Zenit Saint Petersburg, he became the new captain of the club for the 2006–07 season and was voted the club's Player of the Year.
On 1 July 2007, Palermo made an offer of US$7,000,000 for Matuzalém, but it was rejected.
On 2 July 2007, Matuzalém notified in writing Shakhtar of the fact that he unilaterally terminated their contractual relationship with immediate effect. On 5 July, Shakhtar replied Matuzalém and/or his new club should pay the sum in the release clause of €25 million, or Shakhtar would start legal action. The actual phrasing in the contract, however, stated that Shakhtar would be under an obligation to release him if the new club offered to pay that amount. It was not, strictly speaking, a penalty clause.
On 18 July, however, he was presented as Real Zaragoza's newest signing. Shakhtar informed Zaragoza to request the club to pay the fee. After played four games and scoring once, Matuzalém was reported injured since September 2007 and returned in March 2008. He finished the season with just 14 appearances.
Matuzalém's case was considered by FIFA Dispute Resolution Chamber (DRC) on 2 November 2007, which ruled Matuzalém and Zaragoza jointly and severally liable, ordering payment of €6,800,000 to Shakhtar. On 19 March 2008, however, Shakhtar appealed to the Court of Arbitration for Sport (CAS), as the club perceived the fee set by FIFA DRC as too low. On 20 March, Matuzalém and Zaragoza also made an appeal to CAS for the compensation. On 19 May 2009, the CAS ordered Matuzalém to pay €11,858,934 to Shakhtar for breach of contract. The decision was upheld by the Swiss Federal Tribunal. Zaragoza also later paid €500,000 to Shakhtar on 1 September 2010.
Neither Matuzalém or Zaragoza were able to pay the ordered compensation. For this reason, further sanctions, including banning Matuzalém from all football-related activities, were imposed by FIFA on 31 August 2010. This FIFA decision was appealed to the CAS but was rejected on 29 June 2011. The CAS decision was appealed to the Swiss Federal Tribunal. In its decision rendered on 27 March 2012, the Swiss Federal Tribunal annulled the CAS decision, as they found the ban on Matuzalém "a severe infringement of [his] right to privacy". The Tribunal also questioned whether the sanction was likely to lead to the payment of the compensation, which was the stated purpose of the ban. The compensation to be paid to Shakhtar was not affected by this case. This remains the only case where a CAS decision has been overturned based on the merits of the case.
In July 2008, Matuzalém returned to Italy after four years, joining Lazio on a season-long loan with an option to buy at the end of the season for €13 million (plus VAT). Injuries plagued his season, though when fit he established a place for himself in the centre of the Lazio midfield alongside Cristian Ledesma. He claimed some silverware as Lazio won their fifth Coppa Italia, however a booking in the semi-final against Juventus meant he missed the final against Sampdoria. At the end of the season, Lazio exercised the option to keep him on a permanent basis, but for €5,310,000 on a five-year contract.
On 14 March 2010, Matuzalém was injured and missed the remainder of the season. He became a backup of Ledesma and Cristian Brocchi in next season.
On 3 January 2013, Matuzalém was signed by Genoa on a temporary deal. On 24 August 2013 Matuzalém formally joined Genoa on free transfer in 2-year contract.
On 4 July 2014, Matuzalém was signed by Serie B club Bologna in another free transfer.
On 19 September 2015, Matuzalém signed with Serie A side Hellas Verona. His contract with Verona was terminated on 8 January 2016.
Matuzalém signed with Miami FC of the North American Soccer League (NASL) on 20 January 2016. He was released on 12 May 2016.Shakhtar DonetskUkrainian Premier League: 2004–05, 2005–06LazioCoppa Italia: 2008–09Supercoppa Italiana: 2009VitóriaCampeonato do Nordeste: 1997, 1999Brazil Under-17FIFA Under-17 World Cup 1997