Born in São Vicente, Marcelo began his career at Santos, making his first team debut in the 2007 season. He won the Campeonato Paulista with the club that season. He also helped his team qualify to Copa Libertadores semifinals in the 2007 season as well as to quarterfinals in the following campaign. Marcelo made 65 appearances for Santos in all competitions before his contract expired at the end of August 2008.

Marcelo subsequently signed a five-year contract with Polish Ekstraklasa champions Wisła Kraków on 1 September 2008. However, his former club Santos refused to issue his certificate stating that Marcelo has a contract with them until 2011. The court ultimately rejected these claims and Marcelo was successfully registered as a Wisła player.

Marcelo won the Ekstraklasa championship title in his debut season, contributing with 21 matches and three successful strikes. He formed a prominent partnership with Arkadiusz Głowacki in the centre of defence, both were among the three nominees for Ekstraklasa Defender of the Year award in 2009. In the 2009–10 season, Marcelo finished as the club’s third top scorer with a seven goals in the league for the eventual Ekstraklasa runners up.

On 8 July 2010, Marcelo joined Eredivisie side PSV Eindhoven on a three-year deal for an undisclosed fee from Wisła Kraków. He immediately established himself as a regular in the team, playing in 45 matches in all competitions during his first season. In the following campaign, Marcelo won his first trophy with the Dutch outfit, beating Heracles Almelo in the KNVB Cup.

On 10 August 2013, it was announced that PSV had sold Marcelo to Hannover 96 for an undisclosed transfer fee.

On 1 February 2016, Marcelo joined Turkish club Beşiktaş.

On 13 July 2017, Marcelo joined Ligue 1 club Lyon. The transfer fee was an initial €7 million plus €0.5 million in bonuses. Marcelo was the captain for Lyon in the 2018-19 season.