Muir has worked as hard as she ever has to make it to Tokyo after an injury-plagued build-up and compete on the same track where she won Olympic silver four years ago.
The Kinross runner looked comfortable for much of her evening heat, sitting on the shoulder of triple Olympic champion Faith Kipyegon.
But on the final straight, her legs betrayed her, and the veteran finished a disappointing eighth in a time of 4:05.59, two places from qualifying and nearly eight seconds off her season’s best.
A calf tear and Achilles injury earlier had left Muir playing catch-up this season, but she felt she was back in form to challenge for a final in the Japanese capital.
She said: “It was probably the hardest journey I’ve had to get to a championship.
“I’m gutted really. I’ve worked so hard to get back here and I know I’m in really good shape so it’s frustrating to come here and not do what I know I can do.
“I was ultimately aiming to make it to another final and be competitive in that final so to not make it out of the first round is disappointing because it’s not where I am at.
“With 500 to go, I didn’t feel great but there are loads of times in a race when you don’t feel great and you just push through it, so I didn’t think about it.
“I thought sometimes these things happen. That last 100 it made it apparent that it wasn’t ok.
“It’s a bit frustrating when you don’t know why it’s not come together. When there is a reason, it’s easier to accept it. At least I finished the race in one piece.”
Fellow Scot Erin Wallace, in her major championships debut, suffered a similar fate as she finished eighth in the opening heat in 4:06.07.
Wallace ran to her seeding but was disappointed in her performance and admitted she got her tactics wrong.
“My plan was to race from the back, but I ended up surging and jumping over people,” she said after being left behind down the final straight.
“I probably expected it to be a bit faster at the front and so it probably didn’t really play to exactly as I thought it would.
“It’s not like I was a million miles off making the semi, which is probably where I am on paper, so it was solid but just not quite what I wanted.”
Meanwhile, Inverness’ Megan Keith put her Olympic heartbreak behind by finishing a strong 10 th in the 10,000m final.
The 23-year-old finished last in Paris last summer due to an ankle injury and crossed the line in tears.
“On paper I’m happy with the result,” she said after fighting back from four months on the sidelines.
“I wish I could have had more legs under me to fight a bit harder in the closing few laps but I’m I am really happy, especially after a tough one in the Olympics and a tough last year.”
Nicole Yeargin was part of a disappointed mixed 4x400m relay squad that finished fifth in the final.
Yeargin was born in America but races for Britain through her mum, who is from Dunfermline, and ran the final leg after teammates Lewis Davey, Emily Newnham, and Toby Harries.
“My split wasn’t what I wanted it to be, I should have had more confidence in myself to overtake on the back stretch,” she said.
It was a mixed opening day for Great Britain, with Muir’s exit and the mixed relay’s missed medal opportunity the low points.
In more encouraging signs, sprinters Dina Asher-Smith and Daryll Neita both impressed in their 100m heats and are eyeing a medal in today’s final.
Asher-Smith eased up in the final 20 metres and finished second in her race, while impressive Neita clocked a season’s best.
Neita’s 10.94s was the second-fastest of all and she is confident of challenging Asher-Smith and a stacked field, with semi-finals from 12.20pm BST today.
“Hopefully I shock the world,” she said. “This will be just the start.”
In the men’s 100m, Zharnel Hughes, Jermiah Azu and Romell Glave also qualified comfortably.
Hughes was disqualified from the Olympic final here four years ago for a false start and had his heart in his mouth when officials stopped his race for the same issue.
Hughes was relieved to see American T’Mars McCallum was guilty and not him and went on to finish second in 10.06.
USA’s Olympic champion Noah Lyles and Jamaican pair Kishane Thompson and Oblique Seville are the favourites for gold, with both 100m finals from 2.13pm BST.
Follow all the action from the World Athletics Championships Tokyo 25 on BBC.
