[1][2] Mantega served as Minister of Finance from 2006 to 2015 under the presidencies of Luiz Inácio Lula da Silva and Dilma Rousseff.

Upon Lula's access to power in 2003, Mantega was appointed Minister of Planning, and later chairman to BNDES (National Bank for Economical and Social Development).

On March 27, 2006 he was named Brazil's Finance Minister, replacing Antonio Palocci, who resigned in the wake of corruption charges.

In mid-2013, financial-markets commentator David Marsh wrote: Developing-nation economic leaders such as Guido Mantega, Brazil’s outspoken finance minister — who two years ago accused the U.S. of launching “currency wars” through QE and a lower dollar, allegedly to steal a growth advantage —, have had to change their tune.Marsh's comments came as the Federal Reserve's Ben Bernanke was beginning to explore the end of QE and one impact was a "withdrawal of liquidity" from markets such as Brazil's.

[4] Following Lula's victory in the 2022 Brazilian presidential election, Mantega was part of his transition team before choosing to leave.