Fitzgerald left Superior, Wisconsin, at 2:15 p.m. on the afternoon of November 9, 1975, under the command of Captain Ernest M. McSorley. She was en route to the steel mill on Zug Island, near Detroit, Michigan, with a cargo of 26,116 long tons of taconite ore pellets and soon reached her full speed of 16.3 miles per hour. Around 5 p.m., Fitzgerald joined a second freighter under the command of Captain Jesse B. "Bernie" Cooper, Arthur M. Anderson, destined for Gary, Indiana, out of Two Harbors, Minnesota. The weather forecast was not unusual for November and the National Weather Service (NWS) predicted that a storm would pass just south of Lake Superior by 7 a.m. on November 10.

SS Wilfred Sykes loaded opposite Fitzgerald at the Burlington Northern Dock #1 and departed at 4:15 p.m., about two hours after Fitzgerald. In contrast to the NWS forecast, Captain Dudley J. Paquette of Sykes predicted that a major storm would directly cross Lake Superior. From the outset, he chose a route that took advantage of the protection offered by the lake's north shore in order to avoid the worst effects of the storm.

Fitzgerald altered course northward seeking shelter along the Ontario coast where they encountered a winter storm at 1:00 a.m. on November 10. Fitzgerald reported winds of 52 knots (60 mph) and waves 10 feet high. Captain Paquette of Sykes reported that after 1 a.m., he overheard McSorley say that he had reduced the ship's speed because of the rough conditions. Paquette said he was stunned to later hear McSorley, who was not known for turning aside or slowing down, state that "we're going to try for some lee from Isle Royale. You're walking away from us anyway ... I can't stay with you."

By late in the afternoon of November 10, sustained winds of over 58 mph were recorded by ships and observation points across eastern Lake Superior. Anderson logged sustained winds as high as 67 mph at 4:52 p.m., while waves increased to as high as 25 feet by 6:00 p.m. Anderson was also struck by 81 to 86 mph gusts and rogue waves as high as 35 feet.

Some time later, McSorley told Woodard, "I have a 'bad list,' I have lost both radars, and am taking heavy seas over the deck in one of the worst seas I have ever been in."