The Spaniard, who was eliminated in the second round of this competition last year, had previously never been knocked out in the first round of a Grand Slam event.
The opening set remained on serve until 5-5, when Darcis broke to set up the chance to serve for a one-set lead. Nadal broke straight back, but the Belgian moved ahead courtesy of a 7-4 score in the tie-break.
It was a similar story in the second with both exchanging breaks in the latter stages of the set, but once more Darcis came out on top in the tie-break, this time 10-8 to move into a two-set lead.
Nadal, who appeared to be struggling with a knee injury throughout the match, continued to stutter in the early stages of the third set as he lost his opening service game, before Darcis held to go 2-0 ahead.
The Spaniard's best chance of a break came at 4-3, but Darcis managed to hold before serving out the match in style after just under three hours of tennis.