The American fourth seed departed at Melbourne Park on Thursday, when she was beaten by Kaia Kanepi 6-3 6-2.
Victoria Azarenka was the last woman to defend the Australian Open crown in 2013, while Serena Williams was the most recent to go back-to-back at any major, winning Wimbledon in 2015 and 2016.
Kenin, 22, said she struggled to cope with the pressure of defending a grand slam title for the first time.
"Obviously I haven't experienced that. I obviously felt like I'm not there 100 per cent physically, mentally, my game. Everything just feels real off obviously. It's not good," she said.
"I know I couldn't really handle the pressure. I'm not obviously used to this, so right now I just got to figure out how to play at that level that I played at.
"Because like today and those matches, it just hasn't been there. It's weird. I've been practising for two weeks. Luckily I've been able to practice. I felt fine in practice. Just couldn't do that in the game."
Kenin had 22 unforced errors against Kanepi, while she failed to convert any of her seven break points.
After a second loss in as many meetings with Kanepi, Kenin gave credit to the 35 year-old Estonian.
"She obviously played well. I obviously felt like I couldn't find my rhythm. I was obviously way too nervous," she said.
"Yeah, I mean, she played really well. She came up with some good shots. She obviously had a good plan against me. I just couldn't execute my shots."