Father John Misty

In 2006, the independent label Fargo Records released Tillman's first properly distributed solo album, Minor Works, and reissued I Will Return and Long May You Run as a two-disc set the same year. In 2007, Yer Bird Records released his more elaborately arranged fourth album, Cancer and Delirium.

In 2008, Tillman joined Seattle folk rock band Fleet Foxes as their drummer. After extensive touring with Fleet Foxes, promoting their album Helplessness Blues, Tillman played his final show with the band in Tokyo on January 20, 2012.

The UK Music Video Awards is an annual award ceremony founded in 2008 to recognise creativity, technical excellence and innovation in music videos and moving images for music. Tillman has received one award from two nominations.

After signing to independent record label Western Vinyl, Tillman released two albums in 2009, Vacilando Territory Blues and Year in the Kingdom. Tillman said he wrote the title track of Vacilando Territory Blues to describe imagery he associates with his move to Seattle. His brother Zach subsequently moved there as well and is now in the musical group Pearly Gate Music. The following year Tillman released Singing Ax.

Delivered since 2010, the GAFFA Awards (Swedish: GAFFA Priset) are a Swedish award that rewards popular music awarded by the magazine of the same name.

Tillman released the album Fear Fun under his new moniker Father John Misty on May 1, 2012. A couple of months prior to the release of the album a video was released for the song "Hollywood Forever Cemetery Sings" starring Parks and Recreation's Aubrey Plaza. The album was a dramatic departure from any of Tillman's prior releases.

As Father John Misty, Tillman was featured on Kid Cudi's 2013 album Indicud. Tillman wrote an essay about Damien Jurado's recording, Brothers and Sisters of the Eternal Son (Secretly Canadian, 2014). He also wrote the soundtrack for a short film called The History of Caves, directed by his wife, filmmaker Emma Elizabeth Tillman.

The album I Love You, Honeybear was released in February 2015 to widespread acclaim. According to Tillman, it is a concept album about himself and his personal life. Tillman made headlines by covering Taylor Swift's "Blank Space" and "Welcome to New York" in 2015. He claimed to have never listened to the artist prior to recording the covers. This was done as a parody of Ryan Adams, who had released his own version of Swift's 1989, featuring covers of every song. Tillman released a new song entitled "Real Love Baby" on May 19, 2016. He appeared on the song "Saturday Night Inside Out" on The Avalanches' second studio album Wildflower, which was released on July 1, 2016.

Tillman gained media attention on July 22, 2016, after walking off stage at XPoNential Music Festival in Camden, New Jersey, after twenty minutes into his planned fifty-minute performance. Instead of performing his setlist, Tillman walked out and asked, "What the fuck is going on?" He then talked for six minutes about the "numbing" role entertainment plays in our lives and how "stupidity just fucking runs the world because entertainment is stupid." When the audience applauded him he asked them not to and responded by saying, "Maybe just take a moment to be really fucking profoundly sad." He finally played a thirteen-minute piece from his then-upcoming album Pure Comedy called "Leaving LA" which references the frustrations he spoke of during his speech. Tillman then covered Leonard Cohen's "Bird on the Wire" before telling the crowd he loved them and walked off the stage, cutting his performance short. The following day, Tillman explained his performance in an Instagram post, in which he called Donald Trump's speech at the 2016 Republican National Convention a "demonic clown pageant coronation of our next potential Idiot King", which took place the night before Tillman's performance.

On January 23, 2017, the single "Pure Comedy" was released alongside an accompanying music video. The second single released off of Pure Comedy, "Two Wildly Different Perspectives", was released with another music video on January 30, 2017. The third single released was "Ballad of the Dying Man" on February 1, 2017. The fourth single, "Total Entertainment Forever", was released on the night it was performed on Saturday Night Live on March 4, 2017. Pure Comedy was released on April 7, 2017. The album sees Tillman externalize the stereotypical Father John Misty character that he developed through the two previous albums to prevent himself from being constricted to the character's image, using his personhood and experiences to expose his outlook on life.

The Pure Comedy World Tour began in April 2017 and continued into early 2018. During this tour, Tillman mixed the tracks for his next album produced with Jonathan Rado, revealing potential song titles "Mr. Tillman, Please Exit the Lobby" (later shortened to "Mr. Tillman"), "Ouch, I'm Drowning", "Well, We're Only People and There's Nothing Much We Can Do About It", and "Dum Dum Blues". The album explores heartache and was written during a six-week period where Tillman was living in a hotel. Tillman released the lead single, "Mr. Tillman", from God's Favorite Customer on February 20, 2018. The album was announced on April 18 and was released on June 1; its track listing was shared, alongside two further songs, "Disappointing Diamonds Are The Rarest Of Them All" and "Just Dumb Enough to Try".

Tillman has struggled with depression and drug use. He stated in 2017 that he microdoses on LSD daily to alleviate his depression and anxiety. He also stated that he has been diagnosed with PTSD "by three therapists."

British screenwriter and film producer Drew Pearce, who had previously directed the music video for "The Night Josh Tillman Came to Our Apartment", sought out Tillman for his directorial debut Hotel Artemis, when he wanted to cast a musician. Tillman has a small role in the film as a bank robber, and has said that his character "gets his head blown off within, like, 30 seconds." Tillman also contributed to the soundtrack of Hotel Artemis with the song "Gilded Cage", which was released on June 8, 2018, the same day as the film.

On March 23, 2020, Tillman released a live album titled Off-Key in Hamburg, which was recorded at the Hamburg Elbphilharmonie on August 8, 2019, on Bandcamp. All proceeds from the album go to the MusiCares COVID-19 Relief Fund. It has been described by NME as a "high-end luxury offering" and "immaculate".