At eighteen, Ventimiglia studied at the American Conservatory Theater for their summer program,[6] subsequently attending the University of California, Los Angeles as a theatre major.

[8][9] He enrolled at UCLA before landing a role on The Fresh Prince of Bel-Air, guest starring on television series including CSI: Crime Scene Investigation, Sabrina, the Teenage Witch, Law & Order: Special Victims Unit and Boston Public.

[10] From 2001 to 2006, Ventimiglia played brooding teen Jess Mariano on Gilmore Girls; he was introduced in the second season as a leading cast member.

He signed on for a spin-off of Gilmore Girls called Windward Circle which was to be focused on the relationship between Jess and his estranged father (played by Rob Estes), but the proposed series never made it to air.

In the third and final season of American Dreams, Ventimiglia played Chris Pierce, the rebellious boyfriend of Meg Pryor (Brittany Snow).

Ventimiglia also produced and developed a mini web-series called It's a Mall World as part of a marketing campaign for American Eagle Outfitters in 2007.

[18] After working with writers Mark Neveldine and Brian Taylor on Pathology, Ventimiglia appeared in the pair's next film, Gamer.

[21] He played Ned Stax, a former marine, in Frank Darabont's short-lived neo-noir crime drama Mob City for TNT.

"[23][24] Beginning in the fall of 2016, Ventimiglia starred opposite Mandy Moore in the critically acclaimed[25] NBC period drama series This Is Us playing Jack Pearson, the patriarch of a middle-class family in late 1980s/early 1990s America.

[27] For his role as Jack Pearson, Ventimiglia received his first Emmy nomination in the category Outstanding Lead Actor in a Drama Series.

[28] In 2019, Ventimiglia starred opposite Amanda Seyfried in the film adaptation of The Art of Racing in the Rain, based on the novel by Garth Stein.

[37] Ventimiglia completed a United Service Organization tour in July 2008, in support of American troops in Kuwait, Iraq and Afghanistan.