He rose to fame in the early 2000s after appearing on the television series Gilmore Girls (2000–2005) as well as the films Cheaper by the Dozen (2003), Flight of the Phoenix (2004), Cry Wolf (2005) and Friday the 13th (2009).

[4] Although he had originally planned to attend the University of Texas after graduating from high school in 2000, Padalecki decided to move to Los Angeles County, California instead to pursue an acting career.

[1] Padalecki won Fox Broadcasting's 1999 "Claim to Fame Contest"; he subsequently appeared at the Teen Choice Awards, where he met an agent.

Throughout the early 2000s, he appeared in several made-for-television films, including Silent Witness, Close to Home and the Disney Channel Original Movie A Ring of Endless Light.

[17] A month later, Padalecki agreed to guest star on The Boys, the Amazon Prime Video superhero drama helmed by Supernatural creator, Eric Kripke.

Padalecki proposed to her in front of their favorite painting, Joan of Arc, by French realist Jules Bastien-Lepage at New York's Metropolitan Museum of Art in October 2009.

[27] For the second campaign in the Always Keep Fighting series in April 2015, Padalecki partnered with co-star Jensen Ackles to release a shirt featuring both of their faces, to benefit their newly formed joint charitable fund.

[30] During San Diego Comic-Con 2015, more than 6,000 fans surprised Padalecki at the Supernatural panel by holding up candles for him, after having revealed his battle with depression earlier in the year.