Raised in Medford, Oregon, Hamilton moved to New York to study jazz guitar in the early 1980s. While there, he "discovered distortion" and worked with composer Glenn Branca. Hamilton then joined Band of Susans for their Love Agenda album, after which he started Helmet.
Helmet recorded four albums in the 1990s: Strap It On, Meantime, Betty, and Aftertaste. They had moderate chart success, with their last three albums reaching the Billboard top 100, but difficulty keeping his bandmates together caused them to disband in 1999. After Helmet split up, Hamilton started Gandhi, and toured with David Bowie. About this time he recorded with Ben Neill.
He recorded Zulutime (duets with Caspar Brötzmann), played guitar on Ben Neill's Goldbug and Joe Henry's Trampoline, and wrote some music for the movie Heat. Hamilton has also made appearances on "Unbeliever" by Therapy?, "No, You Don't" by Nine Inch Nails, and "God Forbid" by P.O.D..
In 2003, Hamilton and Charlie Clouser recorded the song "Throwing Punches" for the movie soundtrack, Underworld, which marks the first time the song was credited as a Page Hamilton track - mainly because it was about to be released as part of his "solo" album. However, when Hamilton restarted Helmet with an altered line-up in 2004, the song was released as part of the band's comeback album Size Matters.
On 18 July, 2006, Helmet, with further lineup changes, released its most recent album, Monochrome.
Hamilton has also been involved in music production, most notably producing "Distort Yourself" by Gavin Rossdale's band Institute, Bullets and Octane's second album, In The Mouth Of The Young, released in 2006, and the Classic Case album Losing at Life.
During the 2008 tour of Australia, Hamilton told fans that he is going to work on a new Helmet album with the band over the next 18 months.
In 2008, Hamilton recorded guest vocals on the most recent Norma Jean album entitled The Anti Mother. He is featured on the eighth track titled "Opposite of Left and Wrong."