- Because his role in Manhunter (1986) was so emotionally exhausting, he did everything he could to rid himself of the character Will Graham after filming was completed. This included cutting his hair and dyeing this blonde, and shaving off his beard.
- Testified before the Senate Judiciary Committee on increased funding for crime labs.
- One CSI: Crime Scene Investigation (2000) plotline had him pursuing an insane killer played by Tom Noonan, who also played the titular insane killer in Manhunter (1986).
- Calls Long Gone (1987) the most fun he ever had making a movie. He made it instead of appearing in Platoon (1986).
- Has one daughter named Maite Nerea (born 1975) in Mondragón (País Vasco, Spain).
- In March 2002, he became engaged to his longtime girlfriend, Gina Cirone, a biology teacher. The two married in Petrignano, Italy in 2003.
- Declined the offer to produce CSI: Miami (2002), the spin-off of his series CSI: Crime Scene Investigation (2000).
- Attended Bishop Kelly High School in Boise, Idaho. He wears his old football jersey from that school in most of his movies.
- Owns the rights of James Ellroy's crime novel "Clandestine".
- Was offered a role in Platoon (1986), but turned it down because it was a low-paying job. The prospect of going to the Philippines for weeks of training before filming did not appeal to him either.
- An avid fan of the Chicago Cubs, he sings "Take Me Out to the Ball Game" during the seventh inning stretch at Wrigley Field every year and also narrated the documentary Wrigley Field: Beyond the Ivy (2001) about Wrigley Field.
- Has been an ensemble member of the Steppenwolf Theater Company in Chicago, Illinois, since 2008.
- Was cast in To Live and Die in L.A. (1985) after Gary Sinise declined the role. Sinise became the star of CSI: NY (2004), which is the spin-off of Petersen's series CSI: Crime Scene Investigation (2000).
- Longtime friends with Gary Cole. Resided for a time with Amy Morton.
- Has two grandsons named Mazrik William (born October 2003) and Indigo August (born August 2009).
- Attended Idaho State University on a football scholarship, where he found acting.
- Has played the roles of both father and son, Joseph P. Kennedy and John F. Kennedy. Played Joseph P. Kennedy in The Kennedys of Massachusetts. Played John F. Kennedy in Rat Pack.
- Turned down a major role in Michael Mann's Heat (1995).
- He was awarded a Star on the Hollywood Walk of Fame for Television at 6667 Hollywood Boulevard in Hollywood, California on February 3, 2009.
- William's paternal grandfather, Jurgen Petersen, was born in Germany, to Danish parents, Andreas Christian Petersen and Anna Margaretha Ericksen. William's paternal grandmother, Lizzie Ricksher, was of German and French ancestry, while both of William's maternal grandparents, Arthur Cornelius Hoene and Katherine Vera Vollmar, were of German descent.
- Has a production company called High Horse (with friend and fellow CSI: Crime Scene Investigation (2000) producer Cynthia Chvatal).
- Has performed at the Steppenwolf Theater in Chicago.
- Attended the renowned Steppenwolf Company.
- Appears in The Skulls (2000) with Hill Harper. Harper currently co-stars in CSI: NY (2004), the spin-off of Petersen's series CSI: Crime Scene Investigation (2000).
- He was awarded the 2009 Joseph Jefferson Award for Actor in a Principal Role in a Play for "Blackbird" at the Victory Gardens Theater in Chicago, Illinois.
- He was nominated for a 1982 Joseph Jefferson Award for Actor in a Principal Role in a Play for "The Tooth of Crime" at the Remains Theatre in Chicago, Illinois.
- He was nominated for a 1994 Joseph Jefferson Award for Actor in a Principal Role in a Play for "The Night of the Iguana" at the Goodman Theatre in Chicago, Illinois.
- Has two children: twins son and daughter (b. July 5, 2011).
- Was 33 years old when Manhunter (1986) was released. When the film's remake, Red Dragon (2002), was released, his Will Graham successor, Edward Norton, was also 33 years old.
- Has played Missy Crider's father in the miniseries The Beast (1996). Crider later appeared in the second season premiere of CSI: Crime Scene Investigation (2000).
- He was awarded the 1984 Joseph Jefferson Award for Actor in a Principal Role in a Play for "In the Belly of the Beast" at the Wisdom Bridge Theatre in Chicago, Illinois.
- The actor who dubs his voice in Czech, Vladislav Benes, is also the Czech dubbing voice of Pierce Brosnan, Richard Gere, and Noah Wyle.
- Co-presented an award at the 2004 Emmy Awards with Dennis Franz, whose former NYPD Blue (1993) co-star, David Caruso, stars in CSI: Miami (2002), the spin-off of Petersen's series CSI: Crime Scene Investigation (2000).
- Shares his birthday with Larry Drake, who appeared with him in The Beast (1996).
- Has been portrayed in several CSI games.
- His name originates from the Germanic name Willahelm, which was composed of the elements wil "will, desire" and helm "helmet, protection".
- Has played two characters with the surname "Walker". He played Gideon Walker in Return to Lonesome Dove (1993) and Steve Walker in Fear (1996).
- Born on the exact same date as Christine Ebersole (of "Richie Rich" fame).
- His German Voice is Hubertus Bengsch, the Nazi-minded Number 1WO in "Das Boot".
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