Cortini was born in Bologna, and raised in Forlì. Cortini moved from Italy to the United States to study guitar at the Musicians Institute. After graduating, and straying away from the guitar, he decided to focus on keyboards and synths. From 2001 to 2002, Cortini acted as touring guitarist for The Mayfield Four in support of their album Second Skin. While briefly teaching at the Musicians Institute, he saw an ad for open auditions for Nine Inch Nails. Reznor stated that Alessandro Cortini "fit in immediately." Reznor also stated that:
My first thought when Alessandro walked in was that he didn't look like what I had in mind. His presence was intense but gentle, not the "I'm gonna attack you" energy fans might associate with NIN. Then he started, and within 30 seconds I was like "That's the guy!" I never once regretted it. Without taking anything away from Charlie [Clouser], Alessandro is really into playing the studio parts as much as humanly possible.
Cortini toured with Nine Inch Nails from 2005 to 2008, during the band's "Live: With Teeth", "Performance 2007" and "Lights In The Sky Over North/South America" tours. His primary role was that of touring keyboard player, although he also played guitar and bass guitar on some songs. Besides touring with the band, Cortini also contributed to the instrumental album Ghosts I-IV (receiving co-writing credits on a number of tracks) and the 2008 album The Slip. A Modwheelmood remix of "The Great Destroyer" was also released on the Year Zero remix album Year Zero Remixed, and Cortini features in the live DVD Beside You In Time, as well as the music videos for The Hand That Feeds and Survivalism. He left the band at the end of 2008, citing a desire to pursue other projects.
Cortini was also the frontman of Los Angeles band Modwheelmood, which he led with former Abandoned Pools guitarist Pelle Hillstrom. Together they have released two EPs,
? (2003) and Enemies & Immigrants (2006). In 2007, they released Things Will Change, the companion remix disc for Enemies & Immigrants, and they released the first part of their new album Pearls to Pigs, Vol. 1 on December 25, 2007 exclusively as a digital release.
In fall 2006, Cortini contributed to the Musicians Institute's Recording Artist Program by acting as advisor for one-on-one training with students. In 2009, he filled in for Morgan Nicholls (touring member of Muse) while Nicholls took a leave of absence to be with his newborn son.
Alessandro Cortini worked with Ladytron in the production of two of their albums, Velocifero (2008) and Gravity the Seducer (2011). He also co-produced the second track, "We Are the Sea", from the debut album Crystal World (2013) of Ladytron's main singer, Marnie.
In 2010, he contributed electronic production to a song called "Birds of Prey" by pop artist Christina Aguilera, produced by Ladytron. The song is featured on the deluxe edition of her fourth studio album Bionic.
In summer 2010, Cortini formed the project SONOIO. The band name SONOIO comes from the Italian phrase "sono io", which means "it's me", as it is a solo project consisting solely of Alessandro Cortini. In July 2010 SONOIO released the album SONOIO Blue which was followed up by a remix album in December 2010 NON SONOIO. In June 2011 SONOIO released the album SONOIO Red.
Cortini joined How To Destroy Angels, a project consisting of Trent Reznor, Atticus Ross, Rob Sheridan and Mariqueen Maandig, as a touring member. He performs multiple instruments onstage and in addition remixed under his SONOIO moniker their single "The Spaces In-Between", which was used as the show finale for the majority of the tour. In 2013, Cortini returned to Nine Inch Nails as their touring member, and co-wrote the opening track of Hesitation Marks with Trent Reznor.
In March 2017, Nine Inch Nails' official Twitter account announced Cortini would be part of the 2017 summer performance lineup.