He is best known for his role as neurosurgeon Dr. Derek "McDreamy" Shepherd in the ABC medical drama series Grey's Anatomy (2005-15; 2020-21).

He has since starred in several romantic comedy films such as Sweet Home Alabama (2002), Made of Honor (2008), Valentine's Day (2010), and Bridget Jones's Baby (2016).

Dempsey has also taken dramatic roles in Outbreak (1995), Scream 3 (2000), Freedom Writers (2007), Transformers: Dark of the Moon (2011), Thanksgiving (2023), and Ferrari (2023).

Prior to the 2013 24 Hours of Le Mans, Dempsey declared that he would "walk away" from acting if he could and dedicate himself full-time to motorsports.

"[9] An invitation to audition for a role in the stage production of Torch Song Trilogy led to Patrick Dempsey's discovery as an actor.

Dempsey has also made notable appearances in the stage productions of On Golden Pond, with the Maine Acting Company, and as Timmy (the Martin Sheen role) in a 1990 off-Broadway revival of The Subject Was Roses co-starring with John Mahoney and Dana Ivey at the Roundabout Theatre in New York.

He then co-starred in the third installment of the comedy classic Meatballs III: Summer Job, alongside Sally Kellerman in 1987.

This was followed by the teen comedy Can't Buy Me Love in 1987 with actress Amanda Peterson and Some Girls with Jennifer Connelly in 1988.

[10] Dempsey made several featured appearances in television in the 1990s; he was cast several times in pilots that were not picked up for a full season, including lead roles in the TV versions of the films The Player and About A Boy.

He received positive reviews,[11] however, as he portrayed real-life mob boss, Meyer Lansky in 1991 when Mobsters was put on the screen.

Dempsey received an Emmy[12] nomination in 2001 as Outstanding Guest Actor in a Drama Series for the role of Aaron.

In 2004, he co-starred in the highly acclaimed HBO production Iron Jawed Angels, opposite Hilary Swank and Anjelica Huston.

Dempsey has received significant public attention for his role as Dr. Derek "McDreamy" Shepherd in the medical drama Grey's Anatomy opposite Ellen Pompeo.

[10] The relationship his character had with Meredith Grey (Ellen Pompeo) on screen has received a lot of praise and positive reactions.

[13] Universal Pictures acquired the rights to the prize-winning novel The Art of Racing in the Rain in July 2009, for Dempsey to star in.

[23] In November 2020, Dempsey appeared as Derek Shepherd at the start of the series' 17th season for the first time since the character had died in April 2015.

Following his departure from Grey's Anatomy, Dempsey was working on two small-screen projects: a drama The Limit for SundanceTV and a travelogue spy thriller called Fodors.

[25]In 2016, Dempsey starred in the Universal Pictures film Bridget Jones's Baby with Renée Zellweger and Colin Firth,[26] and in 2018 he appeared on Epix television miniseries The Truth About the Harry Quebert Affair.

On February 4, 2020, Dempsey signed on to star as the lead of a CBS political drama pilot Ways & Means, where he would portray a Congressional leader.

[29] In January 2021, it was announced that Dempsey would reprise his role in the Enchanted sequel, Disenchanted, which began production in spring of that year.

[31] In 2023, he portrayed Sheriff Eric Newlon in the slasher film Thanksgiving and Piero Taruffi in the biographical sports drama Ferrari directed by Michael Mann.

In 2014, Dempsey told Reuters in the Hockenheimring support paddock at the German Grand Prix that motor racing was not just a hobby, and had become as much a part of who he is as acting.

"[32] Dempsey, who maintains an extensive sports and vintage car collection, has enjoyed auto racing in his spare time for several years.

He told Porsche Newsroom: "Not much changes in my TV work, but everything changes constantly in motor racing – every lap, every bend and every moment.

In June 2009, Women's Wear Daily reported the launch of a second Avon fragrance named Patrick Dempsey 2.

[56][57] On September 29, 2012, Mexican cable company Cablemás, Megacable and Mexico city's Cablevisión launched an advertising campaign featuring Dempsey as the love interest of a domestic worker who comes across his profile on an online dating site.

[61][62] In January 2013, Dempsey announced that his company (Global Baristas) had secured the winning bid to purchase Seattle-based Tully's Coffee, which had filed for Chapter 11 bankruptcy protection in October.

Dempsey's company will control 47 Tully's locations in the Seattle area, but not the online business, which had been purchased by Green Mountain Coffee Roasters in 2009.

Dempsey filed a lawsuit on behalf of Global Baristas, claiming Michael Avenatti borrowed $2 million against Tully's assets without informing Dempsey, rather than fully financing the coffee chain as was promised, calling the 15 percent interest rate on the loan "exorbitant" and sued for Avenatti to fund Tully's operations and meet its working capital needs, as well as for any damages owed the company.

[74][75] Entertainment Weekly put Dempsey's hair on its end-of-the-decade "best-of" list, saying, "What made Grey's Anatomy a mega-medi-hit?