He's also the first player ranked outside the top 100 to beat the No. 1 man at a Grand Slam tournament since No. 193 Andrei Olhovskiy defeated Jim Courier at Wimbledon in 1992.
Nadal, who owns 14 major singles titles, has appeared in five finals at the All England Club. But he lost in the second round in 2012 and the first round in 2013 — to men ranked 100th and 135th.
In each of Nadal's first three matches this year, he dropped the first set before coming back to win. He again fell behind against Kyrgios, but could not turn the match all the way around this time.
Kyrgios was playing in only the fifth Grand Slam tournament of his career and was the youngest man in the Wimbledon field. In the second round last week, Kyrgios saved nine match points while beating 13th-seeded Richard Gasquet.