Joe Manganiello made his debut in the 2002 American superhero film ‘Spider-Man’ where he portrayed Flash Thompson. The film opened to positive reviews and was a massive commercial success, grossing over $825 million on a $139 million budget. In 2006, he made his first television appearance in the Episode: "Notting Hell" of the American sitcom television series ‘Jake in Progress.’ That same year, he also became a part of the American sitcom ‘How I Met Your Mother’ created by Carter Bays and Craig Thomas. He played the role of ‘Brad Morris’ and remained a part of the show until 2012. He was also seen in television series like ‘American Heiress’ (2007), ‘ER’ (2007), 'Til Death (2008-2010), ‘One Tree Hill’ (2008-2010), and ‘100 Questions’ (2010). In 2010, he joined the main cast of the American fantasy horror drama television series ‘True Blood’ where he portrayed Alcide Herveaux. The series ran for 7 seasons before going off-air in 2014. Manganiello also became a recipient of the ‘NewNowNext Award,’ ‘Saturn Award,’ and ‘Scream Award’ for his performance in the show. In 2012, he appeared in the American romantic comedy film ‘What to Expect When You're Expecting’ directed by Kirk Jones. The film received mixed reviews from critics and grossed over $84.4 million on a $40 million budget. That same year, he also starred as ‘Big Dick Richie’ in the Steven Soderbergh-directed American comedy-drama film ‘Magic Mike.’ The film earned praise from critics and was an amazing box office hit, grossing over $167.2 million on a budget of $7 million.
He continued to star in films like ‘Sabotage’ (2014), ‘Knight of Cups’ (2015), ‘Magic Mike XXL’ (2015), ‘Pee-wee's Big Holiday’ (2016), ‘Smurfs: The Lost Village’ (2017), ‘Justice League’ (2017), ‘Rampage’ (2018), ‘Drunk Parents’ (2019), ‘Bottom of the 9th’ (2019), ‘Jay and Silent Bob Reboot’ (2019), ‘The Sleepover’ (2020), ‘Archenemy’ (2020), ‘Shoplifters of the World’ (2021), ‘Zack Snyder's Justice League’ (2021), and ‘The Spine of Night.’ In 2021, he joined the voice cast of the American animated comedy-adventure television series ‘Big City Greens.’ The third season of the series premiered in October 2021. Manganiello was last seen in the 2022 American teen comedy-drama film ‘Metal Lords’ directed by Peter Sollett. The film earned a 63% approval score on Rotten Tomatoes.