Joined on stage by Bob Marley's grandson Skip Marley, the US singer introduced two skeleton puppets dressed as the US president and the Prime Minister as she performed her latest single 'Chained To The Rhythm'.
The 37th awards, taking place at the O2 Arena in London, saw the late George Michael and David Bowie remembered with the latter winning British Male Solo Artist and the Best Album accolade for his final record, Blackstar.
Perry's explosive performance managed to bring the house down literally as well as figuratively, with one of her backing dancers, who were dressed as model houses, taking a tumble off the stage on to a table.
President Trump's puppet sported a long red tie and clutched the hand of Mrs May, mirroring last month's meeting in the US when the two leaders briefly held hands in an awkward exchange.
Perry campaigned for Hillary Clinton in last year's US election and her latest music video warns against “living in a bubble” as she visits a dystopian theme park.
In the track, Perry sings: “Are we crazy? Living our lives through a lens, trapped in our white-picket fence, like ornaments, so comfortable, we live in a bubble, a bubble, so comfortable, we cannot see the trouble, the trouble.”
Viewers watching on Twitter expressed their amusement over Perry's political performance.
One wrote: “Katy Perry just roasted Trump and Theresa May at the £Brits, I am living.”
Another quipped: “Didn't realise katyperry had hired TheresaMay-MP as one of her backing dancers!”
“OMG IM DYING! Just watched Katy Perry drag Donald Trump and Theresa May on live TV with huge skeleton puppets. She is my idol £SlayQueen,” another Perry fan said.
The ceremony paused to remember fallen stars from last year, including Prince, Leonard Cohen and Beatles producer George Martin before Bowie became the first posthumous winner in the main categories in Brits' history with his two gongs.
The prizes were collected by his son Duncan Jones and actor Michael C. Hall, who stars in the singer's hit musical Lazarus.
Jones said his late father has always supported people who were “a little bit different”, adding: “So, this is for all the kooks and the people who make the kooks.”
Michael, who died on Christmas Day, was remembered with a tearful tribute from his former Wham! bandmates Andrew Ridgley and collaborators Helen DeMacque and Shirlie Holliman - better known as Pepsi & Shirlie.
Ridgley described Michael as a “supernova” adding his death “felt like the sky had fallen in”.
Coldplay frontman Chris Martin then offered a haunting rendition of the Michael's 'A Different Corner', which featured a recorded performance from the late pop superstar.
Home videos and interview clips of the 'Careless Whisper' singer played - including one in which he said he “never wanted to be someone else” - played on a big screen.
The first award of the night went to Scottish singer Emeli Sande who collected her second British Female Solo Artist prize while the British Breakthrough award went to Critics' Choice winner Rag'n'Bone Man.
X Factor alumni Little Mix and indie-pop group The 1975 both received their first ever Brit Awards with the latter being named best British Group.
Little Mix, who opened the ceremony with a rendition of their chart-topping song 'Shout Out To My Ex', won best British Single for the track.
The foursome dedicated the success to their ex-boyfriends, saying: “Cheers to our exes... this is for you lads.”
Adele, who collected four gongs at last year's ceremony, won the Global Success Award, while Beyonce beat her sister Solange to be named best International Female Artist.
Canadian musician Drake won the International Male Solo Artist award and US hip-hop veterans A Tribe Called Quest collected the International Group prize.
Boy band One Direction, who are currently on a break, collected the accolade for British Artist Video for History.
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