Birmingham's Edwards shocked the world when he dethroned Nigerian Usman for the strap via a fifth-round knockout at UFC 278 in August.
Usman, regarded as one of the pound-for-pound best at the time, was well ahead on the scorecards prior to the shock head-kick stoppage with just a minute left on the clock. He won the pair's first meeting via a decision in 2015.
The trilogy fight will take place at London's O2 Arena.
The event will be the first UFC numbered card to take place in the UK since 2016's UFC 204, when Britain's first-ever UFC title-holder Michael Bisping (43) defended his middleweight title against old foe Dan Henderson in Manchester.
Justin Gaethje (34) will fight Azerbaijan's Rafael Fiziev (29) in a lightweight co-main event, while an all-British bout between Nathaniel Wood (29) and Lerone Murphy (31), and a match-up between Scotland's Joanne Wood (36) against Brazilian Carolina Luana (28) will also feature on the card.
