American Simpson claimed his first Major championship in June at the Olympic Club in San Francisco but a repeat of glory already looks a very distant possibility after he failed to recover from a poor start at Kiawah Island.
Simpson bogeyed the opening hole, double bogeyed the third, and was six over by the turn.
Although some damage limitation left Simpson with a score of 79, with the projected cut standing at one over, he will need to see some birdies to keep himself in with a chance of weekend action.
German Kaymer made a triple bogey at the third on the way to his seven-over on the Ocean Course, despite being among the earlier groups who were able to play in much less windy conditions than those that faced Simpson.
Spain's Sergio Garcia, who needs a good showing to boost his chances of making the European Ryder Cup team, shot four-over- par while Lee Westwood, fourth in the world, carded three-over.
Current world number one Luke Donald is also outside the projected cut after shooting 74.