Two Olympic boxing champions from London 2012 put their reputations on the line on Saturday (25 September) at the home of Tottenham Hotspur FC.
Usyk was undisputed world champion at cruiserweight before moving up a weight division two years ago.
Joshua will be looking to add another Ukrainian Olympic gold medallist to his list of victims, having defeated Wladimir Klitschko in a thriller at Wembley Stadium back in April 2017.
After a shock defeat at the hands of Andy Ruiz in Madison Square Garden, which he quickly avenged, the Briton knocked out Kubrat Pulev in December last year to retain his WBA, IBF, WBO and IBO belts.
Now he will be hoping to make his extra weight and strength tell in his 11th consecutive world heavyweight title fight against Usyk who is widely considered one of the best pound-for-pound boxers in the world.
Can cruiserweight king Usyk dethrone heavyweight champ Joshua?
After their gold medals in London, both men made rapid progress in the professional ranks.
Joshua was first to a world title in April 2016, knocking out IBF belt holder Charles Martin in just two rounds to become heavyweight champion in his 16th bout.
Five months later, Usyk was a world champion when he outpointed Poland's Krzysztof Glowacki to win the WBO cruiserweight title in just his 10th pro fight.
He became Ukraine's first undisputed champion in July 2018 when he beat Russia's Murat Gassiev in Moscow before successfully defending his belts against Tony Bellew and then moving up to heavyweight.
If he were to beat Joshua on Saturday night, he would join Evander Holyfield and David Haye in an elite group of boxers to win cruiserweight and heavyweight world titles.
Then he would have the chance to become undisputed heavyweight champion with a fight against the winner of next weekend's WBC title bout between Deontay Wilder and Tyson Fury in the offing.
But Joshua has a significant weight, height, and power advantage over his opponent with 22 wins by stoppage or knockout from his 25 fights. Usyk has been taken the distance five times in his 18 contests and, while his ability is unquestionable, he does lack a knockout punch.
At Friday's weigh-in, Joshua tipped the scales at 17st 2lbs (240lbs; 108.9kg) against Usyk's 15st 11lbs (221lbs; 100.2kg).
The visitor is unperturbed by concerns about Joshua's size saying, "People talk a lot... we'll see on Saturday what happens because the power is in your spirit, it's not about being big or small.
I'm grateful that this is happening. People will remember this fight for a long time. - OLEKSANDR USYK
Joshua admits that has long admired his future opponent, saying, "He was fighting 10 or 12 years as an amateur before he went to the Olympics, and the Worlds... the cream always rises to the top."
He also told Sky Sports, "I respect the man. He has achieved phenomenal things. I'm not someone who will be disrespectful unless someone is disrespectful to me."
Usyk is the heaviest he has been for any fight while Joshua - who was expected by many pundits to weigh in lighter than usual in a bid to counteract the challenger's speed - was not bothered by his own reading.
"I don't really watch my weight. I don't know why there is a big thing about weight. Maybe because we are heavyweights so people look at us at our heaviest.
"As long as you are loose, nimble... loose and heavy, relaxed shots. I should be good. I was heavier and doing it so, now that I'm lighter, I should be able to do it with more ease.
There is no game-plan. Just win. Because you never know what is going to happen when the first bell goes. - ANTHONY JOSHUA
Usyk's last win was a unanimous points decision over former Commonwealth and European heavyweight champion Derek Chisora.
The Briton, who struggled against Usyk's speed, told the BBC that he thinks Joshua's power will see him come out on top.
"One thing AJ has that Usyk doesn't is the knockout punch. It might take six rounds, seven rounds, but I can guarantee you Usyk will get laid out. AJ will get to him."
Tyson Fury, who could face the winner of this bout, thinks it will be closer.
"I'd much prefer to beat Joshua up. It's a bigger fight and people want to see it more.
"Usyk is no mug. People say to me, 'He's too small' and this and that but the guy is bigger than Muhammad Ali, he's bigger than Mike Tyson and he's bigger than Holyfield. He's definitely a good fighter. If he does [win] then he will cost us a few quid."
When is Joshua vs Usyk?
Anthony Joshua against Oleksandr Usyk is the headline bout on the evening at Tottenham Hotspur football stadium, the site of the old White Hart Lane ground which hosted numerous big boxing events for nearly 100 years.
The boxers are expected to make their way to the ring just after 10pm local time in London (UTC+1).
The main card, which also features Lawrence Okolie's WBO world cruiserweight title defence against Dilan Prasovic, starts at 6pm local time.