The Japanese star lifted the last of her four major trophies at the 2021 Australian Open and raised hopes of ending that five-year wait when she downed world number one Aryna Sabalenka in the last 16 at the All England Club.
But Osaka could not back that performance up, slipping to a 7-6(4), 6-4 loss to Czech 10th seed Karolina Muchova.
It was her latest disappointing defeat in the latter stages of a Grand Slam tournament, after losing to Amanda Anisimova in last year's US Open semi-finals.
"I know my results don't show it, but whenever I play a Slam, my intention is to win," said Osaka, who had never before got past the Wimbledon third round.
"Obviously last year I got to the semis (at the US Open). I wanted so desperately to be in the final to have that opportunity, but Amanda played insane...
"This one is a little more upsetting to me because I feel like there was so much more I could have done.
"I think maybe I should find the positive in that because I've gotten to the quarters and I feel like I can still improve so much as a player.
"I feel like in my head I think there's still an opportunity to win a Slam."
Osaka won two Australian Opens and two US Opens between 2018 and 2021 and was ranked number one in the world.
She later took a break to protect her mental health and struggled to find her top form after returning to the WTA Tour.
Osaka then did not play in 2023 after giving birth to her first child.
The 28-year-old took a while to climb back up the rankings after returning, but is now closer to her best, having also reached the French Open last 16 for the first time last month.
"The tournament as a whole, it's the furthest I've gotten here," added Osaka of her Wimbledon run.
"For me, that's a positive. Obviously I would have loved to get a lot farther.
"If I think about my match today, it's hard for me to immediately think of something positive.
"I feel like it's hard because I played so well in my last match, then today I just feel like I didn't play well at all and I didn't have any energy.
"I mean, the score was pretty good for what it was, I guess."
Osaka will next turn her attention to the hard-court campaign, the surface on which she has won all seven of her WTA titles, including those four Slams.
Wimbledon 2026
Wimbledon is taking place from June 29th to July 12th at the All England Club in south-west London. With 128 players in the draw, it is the third of the four Grand Slams of the tennis season and the only one played on grass.
Men's singles draw and results | Women's singles draw and results | All you need to know about the tournament | Find all our Wimbledon coverage here