The 25-year-old beat stars such as Jessie Ware and the late Amy Winehouse to land the solo award.
She then beat off Mumford & Sons, Alt-J, Plan B, and Paloma Faith to collect the premium album prize for her debut Our Version Of Events, which was the UK's biggest-selling album of 2012, with 1.39 million sales.
And in a triumphal finish, she then closed the show with a medley of her hits, before reportedly heading off for a lengthy break from music.
Picking up the first of two Damien Hirst-designed trophies from US star Taylor Swift, Sande said: "This feels amazing. This is incredible and and I'm so happy to win this award."
Receiving the second award from rock legend Bryan Ferry, she added: "I'm an unlikely kind of pop star."
Sande went on: "I don't really know what to say - thank you to everybody who's allowed me to make my music and allowed me to even be considered."
The beaming Sande, who was raised in Alford, Aberdeenshire, collected the prizes at the O2 Arena a year after she won the Critics' Choice Award at the Brits, which kick-started her career. The singer thanked her husband, Adam Gouragine, whom she married last summer.
Sande was little more than a hotly-tipped hope for the future as she collected her Critics' Choice prize at last year's Brits.
But in the past 12 months she has become one of the biggest stars in music and seen around the world thanks to her leading roles in the London 2012 Olympics opening and closing ceremonies.
It has been a busy year for the star, as she also found the time to marry Gouragine in New York towards the end of the summer as well as touring alongside Coldplay.
Sande was born in Sunderland to English and Zambian parents, but was raised in Alford and attended the town's academy. She went to Glasgow University's medical school for four years before signing a music publishing deal in 2010.
Her songwriting prowess saw her working on tracks by Cheryl Cole, Leona Lewis and Tinie Tempah before finding success in her own right.
Sande has credited her father Joel - who ran the school choir - for igniting her passion for music. She has told how he was "naturally musical" and "the sort of person that could pick up an instrument and play it".
Explaining her decision to drop out of her medicine degree, she said in an interview: "Knowing he was behind me was really important to me. I hope I never let him down."
As the Critics' Choice winner at the Brits, she followed in the footsteps of such acts as Adele, Florence + The Machine and Jessie J, who have similarly gone on to huge sales.
Tonight's show opened with rock band Muse, who were backed by a 60-piece string section as they performed their track Supremacy.
Presenter James Corden made reference to last year's show in which he memorably cut off Adele as she collected her best album prize.
He pointed out that Swift had once been cut off mid-speech but there was no chance of such an occurrence tonight. "Not on my watch," he joked.
Mumford & Sons picked up the award for best British group, two years after missing out on the prize when they were previously shortlisted.
It was the band's second Brit win, having collected the best album prize in 2011.
Frontman Marcus Mumford said: "Thanks very much indeed. We weren't expecting that. I don't think we've really taken the opportunity to thank people who have come to our gigs. We were in a group with Muse and One Direction, so it's a surprise."
The best British breakthrough prize went to Ben Howard, who was last year nominated for the Mercury Music Prize.
Collecting the prize from Radio 1 breakfast show host Nick Grimshaw, Howard said: "I'm not very good at speeches. I'm not very good at dancing."
And thanking his mother, he said: "She's rung a lot of old friends to ask them to vote for this."
Ceremony host Corden chatted to members of heart-throb boy band One Direction between performances and teased singer Harry Styles about his reputation for being drawn to older women.
"We've got Sharon Osbourne and Annie Lennox here tonight - who've you got your eye on?" Corden asked.
Robbie Williams, who has landed more Brits than any other artist after collecting 17 as a solo star and member of Take That, was also among performers as he sang his hit Candy.
Howard went on to collect his second prize of the night by taking the best male solo artist award, beating artists such as Olly Murs, Calvin Harris and Richard Hawley.
The singer, who looked taken aback by his second win, said: "This is bizarre, isn't it? I didn't really expect it. I'm quite stoked to even come to the awards, so to come away with two of these is amazing."
Critics' Choice winner Tom Odell was in the audience after picking up his award earlier in the year. "It's crazy to be here," he said.
The evening also featured a much-anticipated performance by Justin Timberlake, who is rejuvenating his musical career after a spell in which he devoted his time to acting. The US hunk, wearing a shiny elegant suit, showcased his new track Mirrors.
Lana Del Rey took the international female award, thanking her record label Polydor for its help in "turning my life into art".
Dely Rey, who's dating Barrie-James O'Neill, of Scottish band Kassidy, went on: "Thank you so much. I live here and I love it and I wrote my record here."
Styles and his boy band played an energetic version of their Comic Relief single One Way Or Another/Teenage Kicks to screaming members of the audience, dancing on a giant pinball machine.
Coldplay were declared best live act, beating the likes of Muse, Mumford & Sons and the Rolling Stones.
Only drummer Will Champion and guitarist Jonny Buckland from the quartet were at the event to collect the prize. Champion thanked fans who had been to see their live shows.
Adele collected the best single prize for her James Bond theme Skyfall - and joked about how she was cut off in her prime at last year's ceremony when the show began to overrun.
In a video acceptance, she said: "Hello everyone - thank you for this Brit Award. Sorry I can't be with you tonight. I'm in LA rehearsing for the Oscars. I won't keep you too long because I don't want to interrupt the best album speech at the end of the night.
"I love you all, thank you so much. I can't wait to come back and see you all. I'm not living here by the way, just in case any of you think that."
Taylor Swift performed her track I Knew You Were Trouble, wearing a long wedding-style gown, which she whipped off to reveal a black lace mini-dress.
US duo Black Keys took the best international group prize, with Foo Fighters star Dave Grohl presenting the award and collecting it on their behalf as they were not able to attend.
:: British breakthrough act - Ben Howard
:: British female solo artist - Emeli Sande
:: British group - Mumford & Sons
:: Live act - Coldplay
:: British male solo artist - Ben Howard
:: British producer - Paul Epworth
:: British single - Adele, Skyfall
:: Special recognition award - War Child
:: Brits global success (for international sales in 2012) - One Direction
:: Critics' choice - Tom Odell
:: International female solo artist - Lana Del Rey
:: International group - Black Keys
:: International male solo artist - Frank Ocean
:: Best album - Emeli Sande, Our Version Of Events