The Russian battled back from two sets down to break Aussie hearts in a five-set thriller in Melbourne.
Ebden took the first set 6-4 as the 23rd seed looked to be going through the motions on the Margaret Court Arena.
Youzhny sought to respond and secured an early break in the second set, but the 25-year-old showed dogged determination to take it to a tie break.
At that point, the 25-year-old blitzed Youzhny 7-0 for a 2-0 lead.
However, the momentum soon shifted in favour of the Russian, who needed just 31 minutes to reduce his deficit to one set.
Both men produced some dazzling winners in the fourth, with Ebden going for power and Youzhny siding with immaculate technique.
Ebden turned the table on his opponent with a beautiful cross-court drop-volley to set up a match point against the serve.
However, he could not take advantage as he carved a backhand into the net.
The Australian then was punished for letting Youzhny off the hook when the Russian broke his serve in the very next game, giving him the chance to serve for a deciding set.
Again Ebden battled back to take the fourth to a tie-breaker but this time it was Youzhny who prevailed.
Ebden's challenge died a death in the final set as Youzhny raced into a 5-2 lead.
He managed to save a match point and force the Russian to serve for the match, which he did to set up a second-round encounter with compatriot Evgeny Donskoy.