Wednesday's auction is the second major art auction in the city in two days.
An auction of works from the estates of heiress Huguette Clark, businessman Edgar Bronfman and other collectors Tuesday at Christie's raised more than $285 million, including $27 million for a Claude Monet painting that has not been publicly exhibited since 1926.
Giacometti's "City Square," a multi-figural sculpture that is estimated to bring $12 million to $18 million, leads the Sotheby's auction, where up to $322 million is expected to be raised.
"Large Thin Head (Large Head of Diego)," Giacometti's sculptural representation of his younger brother, brought $50 million at auction last year. The auction record for any Giacometti work is $103.9 million.
Among other top lots at Sotheby's is Henri Matisse's "Morning Session," a 1924 oil of the artist's assistant, Henriette Darricarrere. It could bring up to $30 million. The current auction record is $48.8 million for his "Black IV," set in 2010.
Sotheby's also has three works by Joan Miro that languished in a New York vault for 50 years.
The Spanish artist created them for the filmmaker and photographer Thomas Bouchard and his daughter Diane. "Untitled, 1947," depicting colorful anthropomorphic forms on a rich blue background, is estimated at $4 million to $6 million.
The other two works are set to go under the hammer at Sotheby's day sale Thursday.
"Water Lilies," Monet's 1907 rendition of his beloved garden in Giverny, France, led the bidding Tuesday in the season-opening auction of impressionist and modern art at Christie's.
Clark, the owner, was a Montana copper mining heiress who died at 104 in 2011. Her father, U.S. Sen. William A. Clark, founded Las Vegas. Christie's is scheduled to sell other pieces from her collection on June 18.
Art from other estates and artists, including works by Edgar Degas, Matisse, Pablo Picasso and Wassily Kandinsky, also sold Tuesday.
Picasso's 1942 painting of his mistress in a purple dress titled "Portrait of Dora Maar" and Wassily Kandinsky's 1909 abstract "Beach Scene," sold for $22.5 million and $17.2 million, respectively.
Both came from the estate of German collectors Viktor and Marianne Langen and were at auction for the first time.