The ethereal Los Angeles-born singer-songwriter is heavily influenced by the counterculture movements of the 1960s and 70s, of which her parents were a part.
But at the same time, the 35-year-old - real name Natalie Mering - believes the obsession with "the good old days" has become "really toxic" for people her own age trying to make it in the "exponentially" changing modern world.
"I do think it's a little harder to have the life that our parents had, and to potentially give that life to children that we may have," she explains, as she prepares to bring her Holy Flux tour to the UK.
"So that changes a lot of things; like when you could buy a house, and this idea of the college degree meaningthis[job or opportunity will follow].
"And I'm so American about it, too," she adds.
"I talk about the good old days because I have such an interesting relationship with the past, being simultaneously like a pagan time travel tourist and also very aware of how toxic the kind of nostalgia we deal with, politically, can be."
While the singer's soothing, timeless folk-rock/baroque-pop sound and aesthetic has been compared to the likes of Karen Carpenter and Joni Mitchell - an artist her mum loves and her dad (both musicians) once went on a date with - the lyrical content of her music is focused firmly on the issues of today.
Songs like It's Not Just Me, It's Everybody, taken from her sumptuously melodic and lusciously layered lockdown album And In the Darkness, Hearts Aglow, find her ruminating on urgent concerns for the planet, the march of machines into human relationships and loneliness.
"Living in the wake of overwhelming changes,"she sings."We've all become strangers / Even to ourselves."
The Times made it its album of 2022, placing Weyes Blood - who has also collaborated with Lana Del Rey, the Killers and John Cale - above artists like Kendrick Lamar, the Arctic Monkeys, Harry Styles and Taylor Swift.
The newspaper described the record as "a set of gorgeous, sweeping, cinematic ballads that delve into love and loss, but end up with buoyant hope".
The Observercalled her recent work "torch songs for the end of time", whilethe Telegraphlabelled the star "the most sophisticated and complex singer-songwriter of her generation".
On the track Children of the Empire, she sweetly urges: "We don't have time any more to be afraid."
Another chronicler of these confusing times, documentary director Adam Curtis, helped to provide the suitably disorientating visuals for third single, God Turn Me Into a Flower.
All in all, the LP constitutes a more personal response to some of the collective traumas laid out in her 2019 breakthrough, Titanic Rising.
"I think with this last record, I was definitely trying to have a little bit more empathy about the position we're all in, versus the kind of anger at our inability to figure out some kind of actionable change," she says.
"Because I think it's such a gridlocked system, it's like we're so locked in to the technology, and I think it's really difficult to feel like you can really make a change in the world."
The lo-fi world of her parents had been that of the "crazy hippies and punks", but they ultimately raised their children as born-again Christians. So church music figured prominently in her upbringing.
The "pendulum swinging" that way for her family, and many other baby boomers in the more conservative 1980s, is something the singer finds "fascinating" to this day.
Having moved with her family from California to Pennsylvania, where she attended high school, Weyes Blood rejected her religious upbringing and set about chasing her own artistic vision across the country - studying, squatting and playing music in Portland and Baltimore.
Early incarnations saw her play bass, keys and sing in noise-rock and punk bands. With one group, she would mix bananas with fake blood, put it on her shirt and rip it open on stage.
It's a far cry from the Laurel Canyon vibes of her best known, recent work, although her metamorphosis into a solo performer did see her produce some spooky ambient drone material.
Nevertheless, it was an important step on her musical journey back to the future.
"There's been a lot of chapters," notes Mering. "I feel like I've lived a million lives. It starts to get weird, the neuroplasticity a little too wild.
"I miss the DIY scene," she adds. "It's changed so much because of smartphone culture and the internet but there was a time when it was so innocent and naÃ¯ve that you felt like you were in the centre of the world.
"It was like the focus was just there, in the moment, and people weren't thinking as much about what they looked like or what it would look like on social media or any of that. So in some ways, it created this weird safe space for crude, raw music and expression."
The arrival of internet culture, she believes, brought with it a "weird qualitative judgement: what is the value of this?, versus just experiencing and enjoying it at face value."
Lately, though, she's been seeing signs of younger people "focusing on a life of creative inspiration" over likes, follows and money. "I still believe that there are communities and people that feel the same way I do. I think that kids are smart and I have a lot of faith in them.
"I've been noticing at my shows that there's young kids, high school age, and they are so unique.
"I say so much about going back in time [but] the kids seem to be very unhinged and free and loose and seeking new forms of community outside of their phones, for sure."
While she may have missed Woodstock festival by a mere half a century, the cosmic pop star did get to play Glastonbury this year, not once but twice.
First, she performed on a candlelit Park Stage, before joining compatriot Caroline Polachek for a duet.
The event, she says, has "one of the best vibes of any festival".
"I feel like America probably had a similar vibe with Woodstock, but we just couldn't keep it going for as long as Glastonbury."
Now, after walking the catwalk in Proenza Schouler's New York Fashion Week show, she'll return to the UK to bring her "well-oiled" concerts to Glasgow, Leeds, London and Nottingham from 11 November.
Her show is like a secular communion, with added jokes between the modern hymns to lighten the apocalyptic mood - a marriage of heavenly sounds and hellish visions.
"It's a pretty wild journey," she nods. "It's kind of a light show, kind of a dance situation. But it's also just a place of catharsis.
"I say my music is like a transportation device. And I would hope that people extract and get different things from it."
Weyes Blood is - to quote US author Kurt Vonnegut - unstuck in time.