The 34-year-old Emmy and Grammy winner- who also acts, directs, writes, produces and DJs – will play the Greenwich venue on 4 November.
It is expected to be the Atlanta star’s largest UK performance to date, months after he won a lead actor Emmy for his comedy series.
Special guest R&B singer H.E.R. – whose real name is Gabriella “Gabi” Wilson – will also perform.
The show will be the second UK appearance for the multi-talented American artist, who headlines at Gunnersbury Park’s Lovebox Festival in July.
His political single, This Is America, which sparked debate about gun violence in the US, reached number 6 in the UK charts earlier this year.
The video – in which a smiling shirtless Gambino dances through a warehouse shooting a hooded man before opening fire on a choir – has been watched about 300 million times since early May.
Described by actor Jamie Foxx as a song that “stopped me in my tracks” at Sunday’s BET Awards, Glover was persuaded to perform a few lines from the song on stage during the ceremony.
Glover has previously hinted that he may soon kill-off his Gambino alter ego, saying at the Grammy’s in January: “I’m making another project right now. But I like endings, I think they’re important to progress.
“I think if a lot of things had death clauses in them we wouldn’t have a lot of problems in the world, to be honest. I think endings are good because they force things to get better.”
Tickets for Childish Gambino’s 02 concert go on sale at 9am on 29 June.