Manganiello was born in Pittsburgh, Pennsylvania, to Susan and Charles John Manganiello. His father, born and raised outside of Boston, MA, is of Italian descent, from Naples. Manganiello was raised in Mt. Lebanon, Pennsylvania. He was a student at St. Bernard School, a Roman Catholic elementary school in Mt. Lebanon, and then attended Mt. Lebanon High School, where he graduated with honors in 1995 and won the school’s Great Alumni Award in 2011. Growing up, he was the captain of his football, basketball, and volleyball teams and went on to play at the varsity level in all three sports. He won the role of Jud Fry in his school’s senior year production of Oklahoma!, and was involved with the school’s TV studio. He would borrow equipment to make films with his friends, and became interested in acting to become a better filmmaker.
After a series of sports injuries, Manganiello auditioned for the Carnegie Mellon School of Drama as a senior in high school. He performed in theater productions and wrote, produced, and acted in a student film entitled Out of Courage 2: Out for Vengeance. He graduated in 2000 with a BFA in acting.
While a student at Carnegie Mellon University, Manganiello appeared in numerous productions in Pittsburgh’s theatre scene, including Ulfheim in Henrik Ibsen’s When We Dead Awaken, Lorenzo in Shakespeare’s The Merchant of Venice for Quantum Theatre, and Joe in the Pittsburgh premiere of The Last Night of Ballyhoo. He moved to Los Angeles, California after graduating from Carnegie Mellon. He quickly signed with a talent agent, and three days later, he auditioned for the role of Peter Parker in the Sam Raimi-directed film Spider-Man (2002). He landed the role of Eugene “Flash” Thompson, Peter Parker’s nemesis, as his first acting job out of college. He reprised the role several years later, making a brief cameo at the end of Spider-Man 3 (2007).
In late 2009 Manganiello was cast as werewolf Alcide Herveaux in the third season of HBO’s True Blood. His work on the show over the next five years would bring him both popular and critical recognition, including the 2011 Scream Award for Breakout Performance – Male and a shared award for Best Ensemble, as well as a Saturn Award for Best Guest Starring Role in Television and a NewNowNext Award. True Blood was his favorite television show before he joined the cast. He was originally brought in by casting for the role of Coot, another werewolf in the series, but was asked by the producers to read for Alcide instead. He familiarized himself with the novels while growing out his hair and beard. He also trained twice a day for months to add muscle to match the description of the character in the books.
Manganiello is also known for his roles in films such as Magic Mike, Magic Mike XXL, Pee-wee’s Big Holiday, What to Expect When You’re Expecting, and Sabotage, among others. In late 2013, he became a published author when his first book, Evolution, was released by Simon & Schuster’s Gallery Books. His directorial debut came in 2014 with the documentary feature La Bare, which he also produced and financed. Manganiello is also known for his role in How I Met Your Mother as Brad. In 2017 he won a Mid-Atlantic Emmy as the narrator of the documentary Pittsburgh Is Home: The Story of the Penguins, which documented the first 50 years of history of the Pittsburgh Penguins hockey team.
Manganiello became engaged to actress Sofía Vergara on Christmas Day 2014 after six months of dating. They married in Palm Beach, Florida on November 21, 2015.