Murray worked at The Second City comedic stage troupe in the early 1970s. He has appeared in numerous films and television shows since then, including as a featured player on NBC's Saturday Night Live from 1979 to 1980 and from 1981 to 1982. He wrote for Jean Doumanian from 1980 to 1981, one of the few cast members to work for all three producers of SNL (Lorne Michaels, Jean Doumanian, and Dick Ebersol). He was a regular on The National Lampoon Radio Hour, a comedy program syndicated nationally to 600 stations from 1973 to 1975. Co-workers on the Radio Hour included Richard Belzer, John Belushi, Gilda Radner, Harold Ramis, and younger brother Bill. He appears in many films with his brother, Bill Murray. However, he has also landed roles in other films. Early on, he appeared in Modern Problems alongside Chevy Chase. Again, years later, he memorably appeared as Chevy Chase's uptight boss, Frank Shirley, in National Lampoon's Christmas Vacation (1989), and co-starred as arcade tycoon Noah Vanderhoff in the film version of Wayne's World (1992). He landed a small role as Assassin Jack Ruby in JFK (1991). He was also seen in the movies Snow Dogs (2002) and 17 Again (2009).

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