McCartney was born in Ardsley, New York to Ginger and Scott McCartney. He began performing in local community musicals at the age of nine, before joining the national tour of The King and I at age ten along with Phil of the Future star Ricky Ullman.

McCartney appeared with The Who's Roger Daltrey in A Christmas Carol at Madison Square Garden. From 1998–2001, McCartney played Adam Chandler, Jr. in the ABC soap opera All My Children, a role for which he earned a Daytime Emmy nomination. He also later starred in the short-lived series Summerland, which aired on the now-defunct WB network for two seasons.

In 2005, McCartney appeared as himself in the Disney Channel show, The Suite Life of Zack & Cody. In 2006, McCartney was also featured as the voice of Roxas in the Disney/Square Enix video game Kingdom Hearts II. In 2007, he starred as himself in the Disney Channel show, Hannah Montana. In 2008, McCartney resumed his voice acting role of the Kingdom Hearts II character Roxas in Kingdom Hearts 358/2 Days. In 2008, McCartney was also featured as the voice of Horton Hears A Who!'s JoJo McDodd. McCartney also voiced Theodore in the 2007 film Alvin and the Chipmunks and the 2009 film Alvin and the Chipmunks: The Squeakquel, in addition to voicing Terence in the 2008 film Tinker Bell.

In 2008, McCartney co-starred along with Elisabeth Harnois in an independent teenage drama feature film, Keith, directed by Todd A. Kessler. It is his movie debut, and features McCartney in the title role. Keith was released on September 19, 2008.

According to Entertainment Weekly in December 2008, McCartney was negotiating to play against type in the role of the Fire Nation's Prince Zuko in M. Night Shyamalan's feature film adaptation of Avatar: The Last Airbender. In February 2009, British actor Dev Patel replaced McCartney, whose tour dates conflicted with a boot camp scheduled for the cast to train in martial arts. McCartney has expressed an interest in directing and producing films and even considered enrolling in a film school.

McCartney appeared as a recurring character in the ABC Family series Greek for several episodes playing a star football talent who joins the fraternity of the starring character Rusty. His character eventually decided to depledge the fraternity after he cited pressures between football and Greek life combined with Rusty stealing away his girlfriend Jordan at the time.

McCartney has provided voice work for the upcoming Kingdom Hearts: Birth by Sleep.

In 1999, McCartney joined the American pop boy band Dream Street, and was a member until 2002. Jesse McCartney has described the experience as a good "stepping stone" for his solo career. The group earned a gold record with their debut CD, and broke up while touring with Aaron Carter. At fifteen, he began work on a solo career with a local band, featuring musicians Dillon Kondor (guitar), Peter Chema (bass), Katie Spencer (keyboards), Alex Russeku (drums), Karina LaGravinese (background vocals), Sharisse Francisco (background vocals), and under the management of Ginger McCartney and Sherry Goffin Kondor, who co-produced his first album, Beautiful Soul.

McCartney released his first solo EP in July 2004. The album featured two songs: "Beautiful Soul","Why Don't You Kiss Her". In 2004, he performed a duet with Anne Hathaway, "Don't Go Breaking My Heart", which is featured on the Ella Enchanted soundtrack.

McCartney's debut solo album, Beautiful Soul, which was two years in the making, was released on September 28, 2004 in the United States and over a year later in Europe. He categorized it as a "pop record" with twists of urban. The album featured four songs that he co-wrote. Beautiful Soul reached number 15 on the Billboard 200. The album has been certified platinum by the Recording Industry Association of America, denoting over one million units of shipment to US retailers; it is his highest-certified album as of early 2009. As of mid-2006, the album had sold more than 1.5 million copies. The album's lead single of the same name reached number 16 on the Billboard Hot 100. McCartney was one of the artist with multiple awards at the 2005 Teen Choice Awards, winning Choice Crossover Artist, Choice Male Artist and Choice Breakout, Male. The following year, he won Favorite Male Singer at the Nickelodeon Kids' Choice Awards.