Phil Mercedes, the world-famous Greatest Pilot of Them All," who has been grounded because of his addiction to alcohol. Wendy Barrie plays Phil's sister Kay, who leaves drafting school to help her struggling sibling get back on his feet, with plans to use her brothers past design skills to keep them both employed. With Phils unrefined airplane designs in her possession. Kay gets her foot in the door at McLean Aircraft, a company at the edge of bankruptcy and looking for radical engineering solutions torevive its fortunes. When a preliminary stress test for a revolutionary wing design drafted by Phil fails, tension is created in the fledgling relationship between Kay and McLeans chief engineer. This prompts Phil to use his prodigious aerial skills to prove his designs are sound and save McLean Aircraft and his professional reputation. Men Against the Sky also features footage of Howard Hughes experimental H-l Racer, which set the transcontinental nonstop speed record in 1937.