The Spaniard suffered his first ever loss in the opening round of a Grand Slam when he slumped to a straight sets defeat to Belgium's world number 135 Steve Darcis.
It was another twist in the 27-year-old's bittersweet relationship with the tournament, where he has been champion twice but also now endured back-to-back humiliating losses.
Twelve months ago, he was defeated in the second round by Czech number 100 Lukas Rosol, a shocker which forced him to take a seven-month break from the tour to rest his increasingly unreliable knees.
Nadal arrived at Wimbledon having wrapped up a record eighth French Open title.
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That was his seventh trophy in nine finals since his return to the tour in February, a run which had also seen him rack up 43 wins in 45 matches.
But eight of those tournaments came on his favourite clay surface, where his knees are not subject to the same crippling pressures.
On grass he needs to bend lower and crouch for the ball while also needing to jam the brakes on his relentless scrapping, jarring the joints even further.
The 12-time Grand Slam title winner immediately withdrew from the Halle grasscourt warm-up in Germany and on Monday Nadal, with white taping again supporting his left knee, was seen to visibly wince with pain.