Jared Padalecki was born in San Antonio, Texas, the son of Sharon L. (née Kammer) (a.k.a. "Sherri"), a high school English teacher at East Central High School, and Gerald R. Padalecki (nicknamed Gerry), a tax supervisor and accountant. His paternal grandfather was Polish. He has an older brother, Jeff, and a younger sister, Megan. He started taking acting classes at the age of 12.

He attended James Madison High School in San Antonio and was named a candidate for the 2000 Presidential Scholars Program. In 1998, Padalecki and his partner Chris Cardenas won the National Forensic League national championship in Duo Interpretation. Padalecki won FOX's 1999 "Claim to Fame Contest"; he subsequently appeared at the Teen Choice Awards, where he met his current manager. Before graduating from high school in 2000, he moved to Los Angeles, California to pursue an acting career, although he had originally planned to attend the University of Texas.

Padalecki's first credit was a minor role in the 1999 film A Little Inside. In 2000, he was cast as Dean Forester on the successful series Gilmore Girls, a role he played until 2005. Throughout the early 2000s, he also appeared in several made-for-television films, including Silent Witness (2000), Close to Home (2001), A Ring of Endless Light (2002) and Young MacGyver (2003).

Padalecki had an uncredited part as a high school bully in 2003's comedy Cheaper by the Dozen. In 2004, he appeared in the Mary-Kate and Ashley Olsen comedy New York Minute, and also had a role in the thriller Flight of the Phoenix. In 2005, Padalecki starred opposite Elisha Cuthbert, Chad Michael Murray and Paris Hilton in the horror film House of Wax, and appeared in another horror film, Cry Wolf. The same year, Padalecki was cast as Sam Winchester on the WB series, Supernatural. The second season of Supernatural began airing on September 28, 2006 on the CW, with the third beginning on October 4, 2007. The show has also been renewed for a fourth season. The show is filmed in Vancouver, British Columbia, Canada. Padalecki also serves as the host of MTV's horror reality series, Room 401. He currently has two movies in post-production. Thomas Kinkade's Christmas Cottage — in which Jared plays Thomas Kinkade — set for release late in November 2008, and Friday the 13th which will open on Friday, February 13, 2009.

He currently lives in Los Angeles, California, but spends most of his time in Vancouver, British Columbia, filming the television series Supernatural. Jared and his long-time girlfriend, Sandra McCoy, got engaged some time in late winter/early spring 2008. A few months after the news about the engagement spread, the couple split for unspecified reasons. Jared is close friends with both Chad Michael Murray, his Gilmore Girls and House of Wax co-star, and Jensen Ackles, who plays his brother Dean on Supernatural.