Brinkley will appear as the jailed killer Roxie Hart for an 11-week engagement from April 4 to June 19 at the Ambassador Theatre on 49th Street.
The 57-year-old model made her acting debut in 1983 opposite Chevy Chase in "National Lampoon's Vacation" and its 1997 sequel, "Vegas Vacation."
She also appeared on NBC's "Mad About You" and hosted Lifetime Television's InStyle Celebrity Weddings.
Brinkley is the latest to play Roxie in the hit musical, now in its 15th year on Broadway. Others include Brooke Shields, Sandy Duncan, Marilu Henner, Bebe Neuwirth, Ashlee Simpson, Michelle Williams and Melanie Griffith.