The man was identified as Jon Santarelli, 53, from Chicago's Lincoln Park.
He was a crew member about the Imedi, a Transpac 52 boat that was racing as part of the Turbo group.
It's unclear if and when the search for Santarelli will resume.
Race officials said they were notified of a man overboard situation around 3 p.m. Saturday.
About 300 boats are sailing the 333-mile route between Chicago's Navy Pier area and Mackinac Island.
The groups had staggered starts, with the cruising class leaving Chicago on Friday and the racing class leaving on Saturday.
Several boats in the Turbo class joined in a grid-pattern search after the man-overboard call was made.
"The search efforts included approximately 20 boats and three helicopters from U.S. Coast Guard, Chicago Fire, Chicago Police and Chicago Yacht Club covering nearly 47 square miles," race officials said. "All competitors in the vicinity immediately suspended their own racing efforts to assist in the search. The man overboard occurred approximately five miles east of Navy Pier, 40 minutes after Imedi began the Race to Mackinac."
Race officials said Santorelli has more than a decade of offshore racing experience. He is well-known in the Chicago sailing community, and is a key member of the Imedi Racing team.
"Our thoughts and prayers are with his family and teammates."
The Chicago to Mackinac is the world's longest annual freshwater sailing race.
Tragedy also struck the race in 2011, when two sailors died.
Mark Morley, 51, and Suzanne Bickel, 41, both from Saginaw, were killed when the boat WingNuts capsized in 4 to 6-foot waves between Charlevoix and South Fox Island. Their deaths were the first caused by the weather or an accident in the race's history.
Conditions were rough on Saturday in southern Lake Michigan. One boat crew reported 20 mph winds and "spitting rain."
The race is known as America's Offshore Challenge. To track the boats, check here.
Last year's race was also tough. It included an incident in which a sailor went overboard and spent an hour in Lake Michigan before he was rescued by another boat's crew.
The 2017 competition started with heavy winds and stormy weather, then the wind switched off and stalled many boats along the last half of the course. Last year saw a record 97 boats "retire," or drop out before reaching Mackinac Island. Some boats were damaged by the wind gusts. One capsized and needed a U.S. Coast Guard rescue.
At 3:00pm today, #CYCRTM Race Committee was made aware of a man overboard alert onboard TP52 "Imedi" in the Turbo Section. USCG, CPD, and CFD have deployed assets to assist in ongoing search. More updates to come.MORE https://t.co/tE1I29Rbb9 pic.twitter.com/x8mqoOU7sS— Race To Mackinac (@RacetoMackinac) July 21, 2018