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Since 2009, O'Neill has been playing patriarch Jay Pritchett on the award-winning ABC sitcom Modern Family, a role for which he was nominated for two Emmy Awards and won two Screen Actors Guild Awards.
O'Neill reenrolled at YSU after being cut by the Pittsburgh Steelers and was one of the first students at the school's then new theatre program. He played Lennie in a stage production of John Steinbeck's Of Mice and Men at the American Repertory Theater in Cambridge, Massachusetts. In 1985, O'Neill appeared alongside Jeff Kinsland in a Red Lobster commercial eating fish and made a brief guest appearance in The Equalizer. In 1986, he was cast as the character of NYPD Police Detective Jimmy "Popeye" Doyle for the planned television series Popeye Doyle.
The Popeye Doyle character originally appeared in the motion picture The French Connection (played by Gene Hackman). The two-hour made-for-television movie/pilot was filmed and shown on network television. O'Neill received good reviews for his performance, and the pilot received good ratings, but the series was not picked up for production.
O'Neill is primarily known for playing the lead role of Al Bundy in Married... with Children, a long-running American sitcom about a dysfunctional family living in Chicago. It was the first primetime television series to air on the Fox Network as a midseason replacement, debuting on April 5, 1987 and concluding June 9, 1997.
During and following the success of Married... with Children, O'Neill appeared in several movies, including The Bone Collector, Little Giants, and Dutch. He also had small parts in Wayne's World and Wayne's World 2, and appeared as Relish the Troll King in The 10th Kingdom. O'Neill made a brief appearance on the comedy variety show In Living Color, playing the "Dirty Dozens" champion who defeats the challenger, played by Jamie Foxx.
He also made a cameo on the sitcom 8 Simple Rules where he was the ex-boyfriend of Cate S. Hennessy (played by Katey Sagal, who portrayed O'Neill's TV wife Peg Bundy on Married with Children).
He also appeared in the movie The Adventures of Ford Fairlane with Andrew Dice Clay and in Cruising with Al Pacino. During the mid-1990s, he had a long string of appearances in commercials for 1-800-COLLECT.
Law & Order franchise creator Dick Wolf cast O'Neill as Sgt. Joe Friday in his 2003 remake of Jack Webb's classic TV crime series Dragnet. The series was canceled by ABC in its second season. O'Neill went on to appear as Governor Eric Baker (D-PA), a recurring character on NBC's The West Wing. Baker, a strong candidate for the Democratic Presidential Nomination, assumed the office of the Vice President under Matt Santos at the end of the series.
O'Neill also played Bill on HBO's television series John From Cincinnati.
In 2008, O'Neill appeared in an advertisement for then-presidential candidate Barack Obama as "Al the Shoesalesman".
In January 2009, O'Neill reunited with David Faustino (Bud Bundy from Married with Children) for two episodes of Faustino's show Star-ving.O'Neill also appeared with the entire cast of Married with Children again when they were honored at the 7th Annual TV Land Award show in 2009, presented by Dr. Phil.
Since 2009, O'Neill has played the role of Jay Pritchett on the ABC sitcom Modern Family, a role that earned him Emmy award nominations in 2011 and 2012.
Starting in winter 2012, O'Neill has lent his voice to TV advertisements for allergy pill Zyrtec.
O'Neill received a star on the Hollywood Walk of Fame on August 30, 2011
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