The 20-year-old won the first set but was beaten 5-7 7-6 (0) 6-2 6-3 by the 19th seed on Court One.
Carlos Ortiz, Dustin Johnson and Brooks Koepka will be happy with their starts, while Phil Mickelson and Sergio Garcia are out of the hunt.
J.T. Poston posted seven birdies and an eagle in his bogey-free 62 to jump out to the Thursday lead at TPC Deere Run.
Bobby Portis had his loyalty to the Milwaukee Bucks rewarded, while some massive rookie extensions were handed out to Dort and Simons.