Following completion of undergraduate pilot training in 2001, Luca flew the AM-X aircraft with the 13th Group, 32nd Wing in Amendola, Italy, from 2001 to 2007. During that time, he obtained all aircraft qualifications, including Combat Ready, Four Ship Leader and Mission Commander/Package Leader.

Within the 13th Group he served as Chief of Training Section and Commander of the 76th Squadron. He was also the 32nd Wing Electronic Warfare Officer.

In 2007, he was selected by the Italian Air Force to become a test pilot. He trained as an Experimental Test Pilot at EPNER, the French test pilot school in Istres.

Luca is a major in the Italian Air Force. He has logged more than 2000 hours flying time, is qualified on more than 20 types of military airplanes and helicopters, and has flown over 40 types of aircraft.

Luca was selected as an ESA astronaut in May 2009.

In February 2011, Luca was assigned as a flight engineer to Italian space agency ASI's first long-duration mission on the International Space Station. He was launched on a Soyuz launcher from Baikonur, Kazakhstan on 28 May 2013.

Luca spent 166 days in space conducting over 20 experiments and took part in two spacewalks and the docking of four spacecraft for his Volare mission. He landed safely back on Earth on 11 November 2013.

Luca was the lead CAPCOM or Capsule Communicator during fellow ESA astronaut Thomas Pesquet’s first spacewalk on his Proxima mission, which took place on 13 January 2017. The spacewalk was completed in 5 hours and 58 minutes.

During the annual press briefing on 18 January 2017, ESA Director General Jan Woerner confirmed that Luca has been assigned a second mission to the ISS in 2019.