In 1999, he completed a master's degree in political sciences at the University of Naples Federico II, Italy, with a thesis on international law.

In 2003, he qualified as Electronic Warfare Officer at the Reparto Supporto Tecnico Operativo Guerra Elettronica [it] (ReSTOGE) in Pratica di Mare, Italy.

Following completion of undergraduate pilot training in 2001, Parmitano flew the AMX aircraft with the 13th Squadron, 32nd Wing in Amendola, Italy, from 2001 to 2007.

In 2014, he became a "cavenaut" serving in ESA CAVES[6] training of the European Space Agency alongside Scott Tingle, Alexander Mirsurkin, Sergey Kud-Sverchkov and Matthias Maurer.

[8] In 2016, Parmitano took part in the first ESA PANGAEA mission, alongside Matthias Maurer and Pedro Duque.

In February 2011, he was assigned as a flight engineer to Expedition 36/37 (a long-duration mission to the International Space Station), which launched aboard Soyuz TMA-09M on 28 May 2013 and arrived at the ISS on 29 May.

[11] On 9 July 2013, he became the first Italian to take part in a spacewalk as he and Chris Cassidy conducted an EVA out of the ISS' quest airlock to install power cables, retrieve material research samples (MISSE-8) and accomplish a number of maintenance tasks.

During the EVA, Parmitano also got to ride on the ISS' Mobile Servicing System for the installation of a couple of radiator grapple bars previously flown up on SpaceX' CRS-2 mission.

The EVA was part of preparations for the new Russian multipurpose module planned to replace the Pirs docking compartment by the end of 2013.

[13] His second EVA on 16 July 2013 was terminated after only 1 hour and 32 minutes, when the helmet of his Extravehicular Mobility Unit suit started filling with water.

Both were assisted by NASA astronauts Christina Koch and Jessica Meir who operated the Canadarm2 robotic arm from inside the Station.