[3][4][5] Marchetti began his professional club career with Torino in 2002, and was subsequently loaned out to Pro Vercelli, Crotone, and Treviso.

In 2005, he spent a season with Biellese, and later played for AlbinoLeffe and Cagliari, before moving to Lazio in 2011, where he won the Coppa Italia in 2013.

A Torino youth system trainee, Marchetti made his professional debut on loan to Pro Vercelli, being then loaned to a number of other Serie C1 and Serie C2 teams in the following years: he spent the 2003–04 season as second choice keeper with Crotone and later Treviso, without making a single appearance with any of these teams.

He started the 2004–05 season as third-choice keeper at Torino, making a single appearance in his time with the granata as a substitute;[citation needed] he then asked to be transferred in January 2005, after Torino signed another keeper, Gianluca Berti, and he was subsequently loaned to Pro Vercelli for the remainder of the season.

Federico Marchetti's continued period of good form during the 2012–13 season saw become one of the club's protagonists; on 26 May 2013, he won the Coppa Italia with Lazio, keeping a clean sheet in a historic 1–0 Rome derby final victory against cross-city rivals Roma.

On 4 July 2023, Marchetti signed a one-year deal with Maltese Premier League champions Ħamrun Spartans.

Marchetti also played in the decisive match against Floriana FC which ended in a 5–0 victory for Ħamrun Spartans, a win which saw them mathematically crowned as champions.

[20] Marchetti made his competitive debut at the 2010 FIFA World Cup, replacing the injured starter Gianluigi Buffon at half time during Italy's opening Group F clash with Paraguay, which ended in a 1–1 draw.

[25] On 14 August 2013, Marchetti was brought on for the second half of an international friendly match, in honour of Pope Francis, between Italy and Argentina, played in Rome.