The Coast Guard said both were unresponsive.
The sailboat WingNuts capsized overnight near the Fox Islands, 60 miles from Mackinac.
A passing sailboat rescued six sailors but could not find the two.
The crew of a competing boat, Sociable, notified the Coast Guard early Monday that the 35-foot sailboat WingNuts capsized west of Charlevoix, during the Chicago Yacht Club's annual Race to Mackinac, Petty Officer George Degener said.
All six of the people recovered by the Sociable crew were wearing life preservers, and they were taken to the Coast Guard station in Charlevoix for evaluation, the agency said.
Authorities did not release the names of the missing crew members. WingNuts is based in Saginaw, and seven of the eight crewmembers registered for the race are from Michigan -- including three from Midland, two from Saginaw, one from Ann Arbor and one from Grandville, according to the race's website. One of the crewmembers listed is from Chicago.
The Coast Guard located the overturned boat and began searching nearby.
A 41-foot boat from Coast Guard Station Charlevoix, a helicopter from Air Station Traverse City and the Coast Guard Cutter Mackinaw were involved in the search. The Coast Guard said 4- to 6-foot waves were reported, and air and water temperatures were in the low 70s.
According to the race website, 355 boats and roughly 3,500 crew members took part in this year's race, which starts at Chicago's Navy Pier and finishes off of Mackinac Island, near where lakes Michigan and Huron meet. The first race was held in 1898, and organizers began holding it every year starting in 1921. This year's race is the 103rd running.
The Associated Press contributed to this report.