The Devils had some nice passage of play but couldn't claw back a slow start in the 25-point loss to the Melbourne-affiliated Demons at North Hobart Oval.
Anna Vrsecky, who went off late after a heavy collision, starred for Casey with three goals in the 8.6 (54) to 4.5 (29) result on Saturday.
Tasmania are slated to enter the AFL and AFLW competitions in 2028, with the expansion franchise's two years in the VFL and VFLW viewed as crucial in the build.
"I had a few tears before the game. It was always going to be highly emotional," Tasmania coach Georgia Walker said.
"The men have had a VFL team before, but this is the first ever here (for the women).
"We've done a lot of reflecting on women's football history. All the mums had their kids running out with them.
"Win-loss is important, but that is a real moment that I wanted them to enjoy."
Former North Melbourne player and Tasmania-born Libby Haines scored the Devils' first goal in the 11th minute with a kick on the run.
"I was lucky enough to get on the end of it from the midfield. It was pretty special, I'll probably remember it for the rest of my life," she said.
"It was a tough pre-season, seven months in the making. It was just good to run out and make history."
The Devils, who had just one pre-season practice game, trailed 28-6 at the end of the first term but managed to reduce the margin to nine points by the start of the last quarter.
Vrsecky struck early in the fourth to give Casey some breathing room - they went on to keep Tasmania goal-less in the fourth.
Mackenzie Banks, the younger sister of Richmond's Sam Banks, booted two goals for the Devils in their strong run during the middle of the game.
Earlier, the men's outfit suffered their second defeat of the season, going down to 2024 and 2025 grand finalists Southport 20.10 (130) to 11.11 (77).
Tasmania started strongly and had a first-quarter lead, before Southport piled on the pain late with an eight-goal-to-three final term.
The Devils were without young defender Jaxon Artemis, who is reportedly set to be snapped up by Richmond at the mid-season AFL draft.
Coach Jeromey Webberley said the 20-year-old had a small calf tear and wouldn't have played irrespective of the upcoming draft.
The loss leaves Tasmania with four wins, two losses and one draw after round eight.
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