Patrick Dempsey made his acting debut in the 1985 American satirical science fiction horror film ‘The Stuff’ where he made an uncredited appearance as an underground stuff buyer. That same year, he also played the role of ‘Corbet’ in the American drama film ‘Heaven Help Us’ directed by Michael Dinner. The film received a mixed response from critics. He continued to star in films like ‘A Fighting Choice’ (1986), ‘Meatballs III: Summer Job’ (1986), ‘Can't Buy Me Love’ (1987), ‘Some Girls’ (1988), ‘Loverboy’ (1989), and ‘Coupe de Ville’ (1990). In 1991, he portrayed ‘Meyer Lansky’ in the American crime film ‘Mobsters’ directed by Michael Karbelnikoff. The film was largely panned by critics and was a box office failure. He next appeared in films like ‘Bank Robber’ (1993), ‘With Honors’ (1994), ‘Outbreak’ (1995), ‘Hugo Pool’ (1997), ‘Denial’ (1998), ‘Scream 3’ (2000), ‘Sweet Home Alabama’ (2002), ‘Lucky 7’ (2003), and ‘Iron Jawed Angels’ (2004). In 2005, he joined the cast of the American medical drama television series ‘Grey's Anatomy’ created by Shonda Rhimes. He played the role of ‘Dr. Derek Shepherd’ which earned him 3 ‘People's Choice Awards.’ While Dempsey remained a part of the show until 2015, he made a brief return to the show in 2020 and parted ways from the series in 2021.
He went on to star in films like ‘Brother Bear 2’ (2006), ‘Freedom Writers’ (2007), ‘Enchanted’ (2007), ‘Made of Honor’ (2008), ‘Valentine's Day’ (2010), ‘Transformers: Dark of the Moon’ (2011), ‘Flypaper’ (2011), and ‘Bridget Jones's Baby’ (2016). In 2020, he grabbed the role of ‘Dominic Morgan’ in the financial thriller drama television series ‘Devils.’ The series completed its second season in May 2022. He will be next seen in the upcoming American live-action/animated musical fantasy romantic comedy film ‘Disenchanted.’