[2] He is known for production and guitar work on albums and singles by many artists, including Fiona Apple, Perfume Genius, Bob Dylan, Feist, Jack Johnson, Marcus Mumford, Laura Marling, Weyes Blood, John Legend, Alabama Shakes, Beck, Conor Oberst, and Bruce Hornsby; as a touring musician with artists such as Lucinda Williams, Band of Horses and Jenny Lewis; and his four solo albums.

[10][11] As a session musician, Mills has collaborated with Conor Oberst, Kid Rock,[12] Weezer, The Avett Brothers, Paulo Nutini,[13] Norah Jones, Carlene Carter, Jesca Hoop, Dixie Chicks, Zucchero, Pink, Lana Del Rey, Dangermouse, Vulfpeck, Fiona Apple,[14] Beck,[15] Marcus Mumford,[16] Ethan Gruska, Randy Newman,[17] Diana Krall,[18] Johnathan Rice, Bruce Hornsby, Julian Casablancas, Jason Boesel, Benmont Tench, Ed Sheeran,[19] Cass McCombs, Foy Vance, The Killers,[20] Andrew Bird, John Legend, Rufus Wainwright,[21] Phoebe Bridgers, and other performers.

[23][24] After spending back-to-back years on tour and in the studio playing on other people's records, Mills made the decision to begin producing in order to explore musical concepts beyond guitar in late 2011.

[37] Mills' producer credits in 2016 and 2017 include the albums We're All Gonna Die from former bandmates Dawes,[38] Darkness and Light by John Legend,[39] Semper Femina by Laura Marling,[40] Eternally Even by Jim James[41] and No Shape by Perfume Genius.

[43] The album was created almost entirely using Roland guitar synthesizers from the 1970s with collaboration from saxophonist Sam Gendel, singer Natalie Mering of Weyes Blood, and violin and string-arrangement virtuoso, Rob Moose, who has appeared on nearly every release Mills has produced.

The first New Deal release, in September 2018, was a soundtrack by Colin Stetson, Canadian-American saxophonist, multireedist, and composer based in Montreal, for the short-lived dramatic television series The First.

On December 5, 2019, Mills teased a clip of "Summer All Over" via an NPR piece by Grayson Haver Currin titled "Songs in an Emergency"[44] that centers around the urgency of climate change.

[48] Released March 3, 2023, Blake Mills composed, performed, and produced all songs on the album Aurora[49] for the North American musical drama streaming television miniseries Daisy Jones & The Six.

In previous shows Mills has been accompanied by musicians including Jackson Browne, Billy Gibbons, Matt Sweeney, Cass McCombs, Jenny Lewis, Charlie Sexton, Benmont Tench, Dave Rawlings, Val McCallum, Tal Wilkenfeld, Mike Einziger, Danielle Haim, Smokey Hormel, Michael Elizondo, Anthony Wilson, and Xavier Mas.