He has also been part of several side projects; these include the Trey Anastasio Band, Oysterhead, Ghosts of the Forest, Phil Lesh and Friends, and Surrender to the Air.

[1] In 1967, Trey was the inspiration for the lead character in the children's book What Does The Cloud Do?, which was written and illustrated by his grandparents, Jean and Cle Kinney.

He graduated from the Taft School along with Steven Pollak, better known as the Dude of Life, who later helped pen such Phish compositions as "Suzy Greenberg", "Fluffhead", "Run Like An Antelope", "Slave to the Traffic Light", and "Dinner and a Movie".

He enrolled at the University of Vermont (UVM) as a philosophy major, where he met original Phish bandmates Jon Fishman, Mike Gordon, and Jeff Holdsworth.

[11] While there, he reconnected with his childhood friend Tom Marshall, and the pair began a songwriting collaboration and recorded material that would appear on the Bivouac Jaun demo tape.

[1] During this time he began a musical association and close friendship with composer Ernie Stires, who taught him composition, theory, and arranging.

Phish is noted for their musical improvisation, extended jams, exploration of a broad range of genres, and original live performances.

Markellis was an early influence on Anastasio and seeing the bassist perform with the Unknown Blues Band was a major reason he decided to attend UVM.

A year later they evolved into The Octet which added Ray Paczkowski on keyboards and Russell Remington on tenor sax and flute; and The Dectet in 2002 through 2004 explored complex arrangements and changes of some songs included on Trey Anastasio, and was an evolved version of the octet, now a ten-piece band with the addition of Peter Apfelbaum on baritone sax and percussion, and Cyro Baptista on percussion.

On August 10, 2008, Trey Anastasio and Classic TAB played a set at the All Points West Music & Arts Festival at Liberty State Park in New Jersey.

Anastasio was featured on the album True Love by Toots and the Maytals, which won the Grammy Award in 2004 for Best Reggae Album, and showcased many notable musicians including Willie Nelson, Eric Clapton, Jeff Beck, Gwen Stefani / No Doubt, Ben Harper, Bonnie Raitt, Manu Chao, The Roots, Ryan Adams, Keith Richards, Toots Hibbert, Paul Douglas, Jackie Jackson, Ken Boothe, and The Skatalites.

On September 27, 2008, Anastasio debuted Time Turns Elastic, an orchestral epic co-created with composer Don Hart, at the Ryman Auditorium in Nashville Tennessee.

On July 30, 2020, Anastasio released Lonely Trip, a collection of original songs written during the COVID-19 pandemic and recorded at his home studio in New York.

[24][25] Anastasio raised $1.2 million of donations from the Beacon Jams for his Divided Sky Foundation, which used those funds were used to purchase a property in Ludlow, Vermont to act as a drug rehabilitation center.

It was intended as a follow-up to Lonely Trip, with Anastasio saying the songs were inspired by further time spent in isolation due to the COVID-19 pandemic: "[Mercy] is like a bookend.

"Guelah Papyrus", featured on Phish's major label debut A Picture of Nectar, includes a Stires-influenced fugue instrumental section called "The Asse Festival" as a bridge between verses.

In the early years of Phish, many of Anastasio's compositions were through-composed, intricate and detailed in conception (for example, "The Divided Sky", "You Enjoy Myself", "The Asse Festival", "The Squirming Coil", "Reba", "Fluff's Travels").

Tom Marshall, a New Jersey computer systems professional and friend of Anastasio since his Princeton childhood, has been his primary songwriting collaborator, acting as lyricist.

Anastasio has often pulled lyrics for his music from large notebooks of poems and prose kept by Marshall, and the pair have taken working retreats during which they wrote and/or recorded demos of new material.

Anastasio's 2012 album Traveler was a collaboration with producer Peter Katis, whose longtime band The Philistines Jr. opened for Phish at UVM early in their career.

[7] Hands on a Hardbody received nine 2012–2013 Drama Desk Awards, tying for most nominations, and winning in the Best Sound Design in a Musical category.

In June 2010, Anastasio appeared as a surprise musical guest on Conan O'Brien's "The Legally Prohibited from Being Funny on Television Tour" stop at Tower Theater in Upper Darby Township, Pennsylvania, where he performed "Alaska."

The highly resonant hollow-body electric guitars built by Languedoc[37] for Anastasio, his Ibanez Tube Screamers, and Ross Compressors are key to his signature tone.

Anastasio has several custom Languedoc hollow-body electric guitars, which make use of set maple necks with 24-fret ebony fretboards and dual Seymour Duncan SH-1 '59 humbucker pickups.

During Phish's 2018 Halloween "musical costume" set, Anastasio deviated from his Languedoc guitars and performed with a white Ed O'Brien model Fender Stratocaster.

Anastasio's guitar influences include Robert Fripp, John McLaughlin, Jerry Garcia, Pat Metheny, Frank Zappa and Jimi Hendrix.

He uses effects such as two Ibanez TS-9 Tube Screamers (with Analogman's Silver Mod) in sequence, the famous Univibe clone the Black Cat Vibe, and a Ross compressor.

In 2005, Martin released a Trey Anastasio signature model acoustic guitar, with a dreadnought body with a curved Venetian cutaway.

Other artists who have recorded or performed at The Barn include Gordon Stone Band, Herbie Hancock, Béla Fleck, Swampadelica, John Patitucci, DJ Logic, Toots & the Maytals, Tony Levin, The Slip, RAQ, John Medeski, Jerry Douglas, Nicholas Cassarino, Van Ghost and Addison Groove Project, Karina Rykman, among others.

Beginning in 2006, The Barn was transformed from a commercial recording facility into a studio environment providing accommodations and work space for artists participating in the Seven Below residency program.