[8] Orianthi independently released her debut studio album, Violet Journey in 2005, composing all the material, contributing guitar, vocals, and drums on most cuts.

Carlos Santana brought Orianthi to Paul Reed Smith's attention which led to her endorsement.

Orianthi relocated to Los Angeles, signed with Geffen Records in late 2006 and struck a management deal with 19 Entertainment.

[6][9] Orianthi has made a commercial for Panasonic, featured in the song "Now or Never" for Bratz: The Movie, played at the Eric Clapton Crossroads Guitar Festival, appeared in The New York Times business section promoting eco-friendly acoustic guitars,[6][10] and opened for Steve Vai in the US.

[9] Following that performance (in addition to recommendations from industry professionals), Michael Jackson's management reached out to Orianthi for an audition for This Is It concerts.

[8][9][14] In regard to being handpicked by Jackson, she stated: I don't know exactly why he picked me, but he watched my YouTube videos and loved them.

She also opened for other artists including John Mayer, Mika, Kid Rock, Daughtry and over 30 dates for Adam Lambert's Glam Nation Tour with former Idol contestant Allison Iraheta.

Orianthi performed at various music festivals and charity functions most notably at the Stand Up to Cancer telethon.

On 12 October 2011, the 5 track EP Fire, produced by Dave Stewart was released as an iTunes download.

The song became very popular and garnered substantial media coverage in India for Orianthi, being cited for her time as Michael Jackson's lead guitarist.

[26][27] Orianthi joined supergroup Hollywood Vampires on the track "Whole Lotta Love" from the band's 2015 self-titled debut album.

In October 2016, Orianthi featured in the 2016 NRL Grand Final pre-game entertainment alongside Richie Sambora.

[28][29] On 29 September 2017, Orianthi and Richie Sambora released a five-song EP called Rise under the name RSO (an acronym of the two members' initials).

[31] Orianthi appears on the track Limelight from Don Felder's American Rock and Roll album, released in April 2019.

Orianthi did two world tours with Alice Cooper, but resigned in June 2014, and was replaced by Nita Strauss.

[34] Orianthi has appeared as a guitarist for other stars including shows with Michael Bolton, Dave Stewart and James Durbin.

[38] In late 2024 it was announced that Orianthi would be rejoining Alice Cooper for the Too Close for Comfort Tour from 31 January through 16 February 2025 filling in for Nita Strauss who was unavailable due to other commitments.