The 39-year-old "Wild" star will receive the annual award on October 30, reported Entertainment Weekly.
"Reese Witherspoon's career is a perfect example of an actress flourishing in today's world... She has continued to impress with her varied choices, ranging from smaller roles in dramas such as 'Mud' to a tour-de-force, Oscar-nominated performance last year in 'Wild'.
"The most appropriate role for Reese Witherspoon today is role model," American Cinematheque chairman Rick Nicita said.
Witherspoon is the 29th annual recipient and joins a long list of honorees that include Eddie Murphy (1986), Robin Williams (1988), Jodie Foster (1999), Robert Downey Jr. (2011) and Matthew McConaughey (2014).
Besides her film work, Witherspoon is active in numerous charities, including Stand Up to Cancer and Children's Defense Fund, where she serves on the board.
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