The 28-year-old world 100m silver medallist will be watched by current holder Tommie Smith, whose record of 19.5seconds was achieved 44 years ago on a cinder track in San Jose, Texas.
"Given the advantage of no bend and the surface is a vast improvement on the cinder track Smith achieved his mark, I'm almost certain Tyson, unless the weather or wind spoils the attempt, will surpass the performance," said Andy Caine, the meeting's elite athlete manager.
Last summer Gay ran the 200m around a turn in New York in a time of 19.58sec which has only been surpassed by Usain Bolt and Michael Johnson.
The Great CityGames programme will also see Olympic 400m gold medallist Christine Ohuruogu competing over 150m, while Sanya Richards-Ross, who succeeded her as world champion last summer, will run in the 200m.
Ohuruogu, runner-up a year ago, will go head to head with fellow Briton Jessica Ennis, the world heptathlon and pentathlon title holder.
The Sunday morning Bupa Great Manchester Run will feature Haile Gebrselassie and Derartu Tulu, arguably the world's two greatest ever distance runners.
Meanwhile, Andrew Lemoncello has angered UKA selectors after withdrawing from Great Britain's marathon squad for this summer's European Championships, less than 24 hours after being named in the team.
Fellow Scot Martin Williams, who recorded a time of 2.17:36 at the Seville marathon in February, has been chosen as his replacement for Barcelona.
Lemoncello's change of heart came after he received a flurry of offers to compete in several major road races following his impressive showing in London last weekend.