Around August 2001, the band Anatomy of a Ghost was formed by John Gourley, Joe Simon, Dewey Halpaus, Nick Simon, and Zach Carothers. Gourley fronted the band having had no previous singing experience. Anatomy of A Ghost quickly gained popularity, but before long, the group broke up. Portugal. The Man was originally started as John Gourley's side project, with Carothers playing bass. Before they had a Drummer, they used drum machines and synth-loops as the backing beat. Gourley and Carothers teamed up with Wesley Hubbard, Nick Klein (former guitar tech for Anatomy of a Ghost) and Harvey Tumbleson, and formed Portugal. The Man. The band left Alaska and went to Portland with the intent of recording and touring. The band recorded demos in the summer of 2004, followed by a U.S. tour that fall. In spring 2005, Klein and Tumbleson left and soon after Jason Christie joined the band. Portugal. The Man's debut record Waiter: "You Vultures!" was released by Fearless Records on January 24, 2006. The album was produced by Casey Bates.

On June 22, 2007, they released their second full-length album, Church Mouth, again produced by Casey Bates, and set out on a full U.S. headline tour with support from The Photo Atlas, Play Radio Play, Tera Melos and The Only Children among others. They then toured Europe and followed it up with another US headlining tour with support from Rocky Votolato and Great Depression during September and October. Following this tour, they joined Thursday on a short east coast tour in November alongside Circle Takes The Square.

In 2008, the band left their label, Fearless Records, and added Ryan Neighbors, their touring keyboardist, as an official member and replacement for Wes Hubbard. On July 30, 2008, it was announced that Portugal. The Man was releasing Censored Colors under its independent record label, Approaching AIRballoons, in partnership with Equal Vision Records. It was released September 16. Zoe Manville, a musician and graphic designer, was involved with this album and has an active involvement on all albums since 2008 including vocals on many of the tracks on Woodstock. John Gourley was also chosen as the recipient of the 2008 AP Magazine's "Best Vocalist of the Year".

In 2009, Portugal. The Man played at Bonnaroo and also at Lollapalooza in Grant Park, Chicago. On April 9, the band announced the next album, The Satanic Satanist, which was released on July 21, 2009. The Satanic Satanist is themed around memories and stories from singer John Gourley's youth in Alaska. The album was recorded with the help of record Producer Paul Q. Kolderie of Pixies and Radiohead fame.

In April 2010, Portugal. The Man announced their signing to Atlantic Records. During the summer of 2010, the band went back into the studio to record their new album with Producer John Hill. They recorded the album in El Paso, Texas, London, England, and San Diego, California. Andy Wallace mixed the album.

On June 6, 2011, Portugal. The Man released a short film featuring the songs "Sleep Forever" and "Got It All (This Can't Be Living Now)" from their album, In The Mountain In the Cloud. Produced by Richard Hutchins and directed by Michael Ragen, the film features 13 minutes and 16 seconds of Alaskan wilderness intertwined with scenes of John Gourley dog sledding before he is forced to travel by foot after his dogs abandon him.

On April 3, 2012, it was announced via Facebook that keyboardist Ryan Neighbors would be leaving the band to pursue his own music career with his new project Hustle and Drone. He was replaced by Kyle O'Quin. Drummer Jason Sechrist was replaced by former child actor and Drummer Kane Ritchotte shortly after Neighbors' departure.

In 2013, singles from Evil Friends, including "Evil Friends" and "Purple, Yellow, Red and Blue", were remixed by artists including Bear Mountain, Terry Urban and Passion Pit. Airing on September 26, 2013, in the United States, Taco Bell featured Portugal. The Man's song "Evil Friends" to advertise their Grilled Stuft Nacho item in a television commercial entitled "Getaway".

The band's song "Heavy Games" was featured on a trailer for the fourth season of The Walking Dead. The song has since been included in the show's Soundtrack album that was released on March 25, 2014. The band's song "Sleep Forever" was featured on the Shameless episode, "Emily", which aired on March 30, 2014. The song "Hip Hop Kids" was used in the short film CyberBully, which aired January 15, 2015. A remix version of their song "Evil Friends" (Jake One Remix feat. Danny Brown) was used as the end credits for an episode of Silicon Valley that aired on June 7, 2015. The song "Waves" was used in the TV series "American Crime" premiere episode, that aired on March 5, 2015. Their song "Feel It Still" has been used in many advertisements, including commercials for the iPad Pro, Vitamin Water, and YouTube TV. In 2018 the band performed at the March for Our Lives Portland.

In November 2014, Portugal. The Man were in the studio recording their eighth album with Mike D from The Beastie Boys producing. The band also actively updated their Instagram account with pictures of them in the studio with Mike D, as well as showcasing small teasers of what their new album would sound like. Mac Miller was also shown working with the band as well. The first week of May, 2015, the band released teasers on social networks of what appeared to be new music with a Latin twist with huapango guitars, dream synths and drums machines. On May 5, Portugal. The Man released a Spanish version of "Purple Yellow Red and Blue" covered by a Mexican-American band called The Chamanas on their official YouTube channel to celebrate the Mexican festivities (Cinco de Mayo). On December 31, 2015, Portugal. The Man posted to their website that they had completed two records followed by separate hashtags #Gloomin + #Doomin. However, on February 3, 2016, the band tweeted from their official account that the new record would be entitled Gloomin + Doomin. In February 2016 Portugal. the Man were featured on the Yoko Ono collaboration album Yes, I'm A Witch Too performing "Soul Got Out of the Box".

The video for "Noise Pollution" was released on December 1, 2016.

The video for "Feel It Still" was released on March 6, 2017, and received attention for its imagery of a burning newspaper titled Info Wars.

"Live In The Moment" became a #1 track on the Billboard Alternative Songs chart during the week of March 26, 2018. It additionally gained the honor of the track with the most spins (plays) during a week's time, that has ever been recorded on Alternative radio at 3,503.