In April 2012, at a sold out show at the Lifestyle Communities Pavilion, they announced their signing to Atlantic Records subsidiary label Fueled by Ramen. On July 17, 2012, they released their debut Fueled by Ramen recording in the form of a three song EP, entitled Three Songs. In August 2012, they embarked on a short tour with Neon Trees and Walk the Moon. They worked with Greg Wells, producer of Adele and Katy Perry, on their first full-length album on the record label Fueled by Ramen, Vessel. It was released January 8, 2013 and reached No. 58 on the Billboard 200, No. 42 on the Digital Albums chart, No. 17 on the Internet Albums chart, No. 15 on the Rock Albums Chart and No. 10 on the Alternative Albums Chart.

The group currently has their first radio hit in America, "Holding on to You", which has reached 11 on the Billboard Alternative Songs chart; additionally, the singles "Guns for Hands" and "Lovely" reached No. 21 and No. 67, respectively, on the Japan Hot 100.


Twenty One Pilots performing in 2012
On November 12, 2012, the official music video for "Holding on to You" was released on YouTube. Sequentially in 2013, music videos for "Guns for Hands" and "Car Radio" were uploaded on January 7 and April 19.

In May 2013, Fall Out Boy announced that Twenty One Pilots will be touring as opening acts on the Save Rock and Roll Arena Tour the following Fall.

On August 8, 2013, Twenty One Pilots performed "House of Gold" on Conan in their late night debut. On October 2, the music video for the song was uploaded to YouTube.

On December 24, Christmas Eve, Tyler Joseph participated and sang "O come, O come, Emmanuel" at Five14 Church's Christmas With the Stars in New Albany, Ohio. The official video of the performance was uploaded to YouTube on February 14, 2014. He also performed a magic segment with David McCreary for the show.

On December 31, New Years Eve, the music video for Twenty One Pilots' song, "Truce", was uploaded via YouTube.
Also in December, the official music video for "Migraine" was uploaded via YouTube (only limited to the UK region) and Vimeo. However, both were deleted shortly after. On March 17, the band performed a set at the mtvU Woodie Awards during SXSW.

The updated version of the song "Lovely" was found on the bonus tracks of Vessel, which became available solely in the UK. It was a higher-quality remake of the song from Regional at Best