Early life
He is the son of actors Patty Duke and John Astin (although his biological father is Michael Tell, a Jewish-American writer who divorced Patty Duke shortly before her marriage to Astin). At the time of his birth, it was widely assumed that his biological father was Desi Arnaz, Jr., although this has been proven to be incorrect. Sean is the older brother of Mackenzie Astin, also an actor (in The Facts of Life).

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Film career
Astin has gained much of his acting fame from several major roles. At age 13, he debuted on the silver screen as Mikey in The Goonies (1985). He had a small role in 1989's The War of the Roses and in 1993 got the memorable part as the title character in Rudy. Astin most recently played Samwise Gamgee in Peter Jackson's the Lord of the Rings movies.

In 1994, he directed and co-produced (with his wife, Christine) the Academy Award nominated short film Kangaroo Court.

While working on The Two Towers he persuaded a number of fellow cast and crew members, including director Peter Jackson, to act in or work as crew on his short film, The Long and Short of It (2003), which takes place on a street in Wellington, New Zealand. The film premiered at the Sundance Film Festival, 2003, and appears on the "standard edition" DVD of The Two Towers as an extra feature together with a "making of" video.

Astin has signed on to guest star in the fifth season of the FOX drama 24.

  Before the Devil Knows You're Dead (2005) (announced) .... Bobby
Mark Twain's Greatest Adventure: 'It's a Matter of Time' (2005) (pre-production) .... H.G. Wells
The Final Season (2006) (pre-production) .... Kent Stock
Cowboys for Christ (2006) (pre-production)
Borderland (2005) (filming) .... Randall
Click (2006) (post-production) .... Bill Rando
Astérix et les Vikings (2006) (post-production)
Cat Tale (2006) (post-production) (voice) .... Rover
Kingdom Hearts II (2005) (VG) (voice) .... Hercules
"Into the West" (2005) (mini) TV Series .... Martin Jarrett
"Hercules" (2005) (mini) TV Series .... Linus
Smile (2005/I) .... Mr. Matthews
Bigger Than the Sky (2005) .... Ken Zorbell
Slipstream (2005) .... Stuart Conway
Marilyn Hotchkiss' Ballroom Dancing and Charm School (2005) .... Joe Buco
Thanks to Gravity (2005) .... Coach Amal
Men of Valor (2004) (VG) (voice) .... Pat 'Mouth' Hodges
Balto III: Wings of Change (2004) (V) (voice) .... Kodi
Elvis Has Left the Building (2004) .... Aaron
Party Wagon (2004) (TV) (voice) .... Randall P. McDuff/Josiah
50 First Dates (2004) .... Doug Whitmore
"Jeremiah" (2002) TV Series .... Mister Smith (2003-2004)
The Lord of the Rings: The Return of the King (2003) .... Sam
The Lord of the Rings: The Two Towers (2002) .... Sam
Kingdom Hearts (2002) (VG) (voice) .... Hercules
The Lord of the Rings: The Fellowship of the Ring (2001) .... Sam Gamgee
Dish Dogs (2000) (V) .... Morgan
The Last Producer (2000) .... Bo Pomerants
The Sky Is Falling (2000) .... Mr. Schwartz
Icebreaker (1999) .... Matt Foster
Deterrence (1999) .... Ralph
Kimberly (1999) .... Bob
Boy Meets Girl (1998/II) .... Mike
Bulworth (1998) .... Gary
Courage Under Fire (1996) .... Patella
The Low Life (1995) .... Andrew
Harrison Bergeron (1995) (TV) .... Harrison Bergeron
Safe Passage (1994) .... Izzy Singer
Teresa's Tattoo (1994) (uncredited) .... Step-Brother
Rudy (1993) .... Daniel E. 'Rudy' Ruettiger
Where the Day Takes You (1992) .... Greg
Encino Man (1992) .... Dave Morgan
Toy Soldiers (1991) .... William 'Billy' Tepper
The Willies (1991) .... Michael
Memphis Belle (1990) .... Sgt. Richard Moore
The War of the Roses (1989) .... Josh at 17
Staying Together (1989) .... Duncan McDermott
Like Father Like Son (1987) .... Clarence aka Trigger
White Water Summer (1987) .... Alan
The B.R.A.T. Patrol (1986) (TV) .... Leonard Kinsey
The Goonies (1985) .... Mikey Walsh
The Rules of Marriage (1982) (TV) .... Charlie Hagen
Please Don't Hit Me, Mom (1981) (TV) .... Brian Reynolds