Gaming

Assassin's Creed Odyssey female lead is canon, although you have the choice to play the male as well.

Mirror's Edge is a good one I haven't seen mentioned yet. A bit older by this point but it was a fun one.
Transistor is another great one. The gameplay was fine but the art and sound is incredible.

Scrolled through the comments, how has no one not mentioned A Plague Tail? Amazing story from a woman's perspective

I'm having a great time finally getting into What Remains of Edith Finch.

Control is excellent

Not female, but the protagonist of Outer Wilds is nonbinary, as is their entire species.

Silent Hill 3 has a great female protagonist imo, but you have to play Silent Hill 1 to get the gist of the story in 3.

All the Metroid games, especially the 2D ones. If you like a good metroidvania, well, you can't go wrong with the game that created the genre.

I did not see Celeste mentioned, but if you're at least one bit into platforming, this gem is an absolute must-play. And must listen, I have the OST on repeat since it came out.

If beat them all are your jam, you need to play some P* games, and the ones with a female protagonist are the Bayonetta. Heavily sexualized, but to a point where it becomes some kind of parody of itself, you have to embrace the aesthetic. The rhythm is frantic, the scenario barely understandable, the action way over-the-top, and the combat gameplay tight as hell.

In more standard AAA waters, the two Tomb Raider reboots are pretty good, although a bit heavy on male-gaze.

Back to the indy side, What Remains of Edith Finch is a first person narrative game, in which you'll play as different characters. But the main ones are girls, and it matters in the plot.

Most games I can think of have been mentioned, but I found Signalis to be an interesting experience assuming you can get past the annoying inventory management

Can I suggest some great novel games?

**VA-11 HALL-A: Cyberpunk Bartender Action **

• play as a bartender and change outcomes of stories by providing different drinks

Fatal Twelve

• death game, mystery, lesbian couple as main character, one of the best

Jade from Beyond Good and Evil.

Great list from @mint@beehaw.org, just a few more:
Gris is an absolute gem.
The A Plague Tale duology is also up there (with Requiem being my favourite game of all time, so I'm extremely biased, sorry / not sorry :D).

Trying to find some that haven't been talked about yet:

Echo. It's a fantastic experimental infiltration game with an AI that adapts to your way of playing. The setup is very impressive.

Pathologic: one of the three playable characters (the Changeling). It's a bizarre russian game, with an unique world, and messy gameplay. Can't recommend it enough.

Va11 Hall-A: chill bartending game in a cyberpunk setup.

The Blackwell series: comfy, kind of amateurish point and clicks by Wadjet Eye. I like them very much.

Transistor: weirdest game by Supergiant. You play as a redhead with a talking sword. I don't remember much about it except that it was good.

The Fall: (pushing it a little bit, since the protagonist is an AI, but I've always seen here as female.) Criminally underrated puzzle games, disguised as metroidvanias.

Eliza (by Zachtronics): the only visual novel I enjoyed. It's hard to explain, it's about AI, burnout, whether tech dehumanizes people, and solitaire.

Hedon Duology: for something completely different, it's a slightly kinky retroshooter, with amazon Orcs fighting demons.
It may sound a bit dumb, but it's excellent. Huge levels, interesting worldbuilding, and a gameplay based on exploration, puzzles as well as shooting.

There's probably a ton more, but that's all I can think about at the moment.

Cyberpunk!

Don't see it mentioned yet, it's an older game but Remember Me is pretty good

Aquaria

A very well put together Metroidvania. The map is very fun to explore, good boss fights, great music, and interesting story.

Resident Evil Remake 2 and 3, great games with both male and female protagonists!

Some not yet mentioned.

• Heaven's Vault
• Mirror's Edge
• Portal (technically, though she's mute so not that it matters much)
• Slime Rancher
• Spiritfarer

Returnal is a great game if you like roguelite mechanics. Great gameplay, art design, and sound. The haptics on the PS5 are excellent too.

It's older, but The Longest Journey is good. Unfortunately, the final game in the series kinda sucks.

While it's an ensemble, most people would agree that the main character of Final Fantasy VI is a woman—they just might disagree about which woman is the lead.

I also liked the first Xenosaga game, but again, it's a series that goes pretty badly downhill.

The Mass Effect series is still my favorite, you can choose your protagonist to be female and the game will adapt accordingly. Or Dragon Age if you are more into fantasy.

A group of developers have created a version of the game and it's sequels that runs on modern machines: http://nolfrevival.tk/

Edit: this was meant as a reply to @KIM_JING_JUICEBOX 's comment. No One Lives Forever is a whip smart spy FPS that nails the Bond aesthetic but stars an unforgettable female protagonist, Kate Archer. Download it for free above.

Night in the Woods is objectively the best game ever made by any measure. Tacoma and Gone Home are amazing too.

I mean I dunno, it depends on what kind of games you like, surely?

Whoa whoa whats wrong with Senua?

Plague Tale:Innocence and Requiem

Surprised no one has mentioned Tomb Raider yet. Others not yet mentioned:

• Assassin's Creed: Liberation, and Chronicles: China
• Beyond: Two Souls
• The Last of Us Part II
• inFamous: First Light

Ms Pac Man obviously

It Takes Two has a great protagonist

Shadow of the Tomb Raider. Lara Croft is still a thing...

Stardew valley is fun