Branch was born seven weeks premature in Phoenix, Arizona, and was named after The Beatles' song "Michelle". Her father is of Irish ancestry while her mother was born in Holland; her maternal grandmother was from East Java and was held in a Japanese concentration camp during World War II, while her maternal grandfather was Dutch. She has an older half-brother, David, and a younger sister, Nicole.

Branch started taking voice lessons at a local university when she was 8 years old. She received a guitar for her fourteenth birthday from her uncle. She locked herself in her room and taught herself chords; within a few days she had composed her first song. She focused on the arts during high school, and was writing songs extensively. She attended Red Rock High School in Sedona but with the support of her parents, decided to continue her high school education through homeschooling, which allowed her to follow her dreams of becoming a singer-songwriter. She had begged her parents to allow her to leave regular high school, and one night at dinner she asked why she had to go back to school, and to her surprise, her father replied with, "Yeah, why does she?" She played clubs for years and released her debut album Broken Bracelet independently in 2000.

She signed a record deal with Madonna's record company Maverick while opening for Hanson in December 2000. Her first album under Maverick, The Spirit Room, was released in August 2001 and went on to sell over one million copies in the U.S. The single "Everywhere" became a worldwide top-twenty hit, and was followed by the U.S. top-ten hit "All You Wanted" and the top-forty single "Goodbye to You". Branch was frequently compared (both positively and negatively) to other singer-songwriters like Alicia Keys, Avril Lavigne, and Vanessa Carlton who rose to prominence at around the same time as she. In 2002 Branch was the lead vocalist on Carlos Santana's song "The Game of Love", which became her first single to reach the U.S. top five; it went on to win a Grammy Award for "Best Pop Collaboration with Vocals".

In 2003 she released her second full-length album, Hotel Paper, which became her second RIAA-certified platinum album but was met with mixed reviews. The lead single "Are You Happy Now?" became another top-twenty hit for Branch in the U.S., but follow-up singles "Breathe" and "'Til I Get over You" failed to achieve substantial success. In Mexico, on May 23, 2004, Branch married her tour band's bass player, Teddy Landau. Later that year she hosted MTV's Faking the Video alongside Nick Lachey and JC Chasez. She gave birth to a 7lb. 12oz. (3.5 kg) baby girl named Owen Isabelle on August 3, 2005.

In July 2005 Branch announced the completion of an album with country singer Jessica Harp. The longtime friends and collaborators dubbed themselves The Wreckers, and created an album combining Branch's pop-rock music with Harp's country-folk style. The album was originally due for release in June 2005 but was delayed because of promotional reasons.

One of the songs Branch co-wrote with Harp for the album was featured on the original soundtrack to the WB television teen drama One Tree Hill. Branch and Harp made a brief appearance as themselves on One Tree Hill, and then went on a month-long concert tour with Gavin DeGraw and One Tree Hill stars Tyler Hilton and Bethany Joy Lenz. Branch has sung on the television shows Buffy the Vampire Slayer (in the episode "Tabula Rasa") and Charmed (in the episode "Centennial Charmed").

Branch closed down the message boards for The Wreckers' official website in December 2005, after being displeased by comments posted there. The Wreckers' first single, "Leave the Pieces", was released in March 2006; the album Stand Still, Look Pretty was released the following May. During this period, they joined country music stars Rascal Flatts and Gary Allan on a sold out U.S. tour.

Branch has written songs for other artists, including one for Mandy Moore's next album. As of 2006, her biggest hits ("Everywhere", "All You Wanted", and "Are You Happy Now?") continue to be played in recurrent rotation on CHR and Hot AC radio stations.

Branch writes or co-writes all of her own material, and her music influences are The Beatles, Led Zeppelin, Queen, Aerosmith, Cat Stevens, and Joni Mitchell. While her musical tastes lean more toward older musicians, she also enjoys contemporary bands such as Soundgarden, Nirvana, Stone Temple Pilots, Metallica, and Silverchair and current songwriters including Lisa Loeb, Sheryl Crow, and Patty Griffin. She has also expressed her admiration for classical music.