Over 360 athletes from 40 nations will take part in athletics, track cycling, swimming and wheelchair basketball.
Highlights include Tanni Grey Thompson and amputee sprinter Oscar Pistorius in action, as well as China's debut in women's basketball.
Dave Titmuss' side claimed a dramatic overtime victory over Australia 12 months ago and will face them again, along with Paralympic champions Canada and Sweden at the Manchester Velodrome.
But Team GB, who won bronze at the 2004 Paralympics, will be without key players Simon Munn, Jon Pollock and Colin Price, as well as recently retired Ade Adepitan.
Former GB captain Dan Johnson fears the men's team may find this year's competition a much more difficult task.
"I think Great Britain will have a tough task in Manchester, given they are missing a few players," said Johnson, who will be commentating on the event for BBC Television.
In the women's event, GB will also be hoping to impress as they attempt to bounce back from last year's defeat to France in the final.
Spain return to the competition for the second year and are joined by Mexico, who finished sixth in Athens, and China, who are making a rare trip overseas.
While China remain an unknown quantity on the international scene, GB women's coach Garry Peel is expecting the main threat to come from Mexico.
"We don't know anything about China," Peel told BBC Sport. "I think they might just be a development team.
"But I know the Mexican team came sixth in Athens, so they're quite a decent team."
Dame Tanni Grey Thompson, David Weir, Danny Crates and Shelly Woods leads a crop of top home-grown talent at the athletics finale on Sunday.
Britain's most successful Paralympian, Grey Thompson returns to the spot of her T53 100m and 400m victory last year.
Also in action is Athens 2004 gold medallist Crates, keen to gain revenge for missing out on gold in the T46 800m last year.
Wheelchair racer Weir, fresh from his blistering victory in the London Marathon, is relishing the chance to prove his ability across all distances in the T54 100 and 200m sprints as well as the 1500m.
He said: "I'm feeling pretty confident ahead of the Paralympic World Cup. I need to push it up a little on my sprints but I'm confident that I can race well at any speed now."
Woods renews her rivalry with Italian Francesca Porcellato as she competes in the T54 200m and 800m.
The 19-year-old was second behind Italian Porcellato at the London Marathon for the second straight year.
She said: "There's going to be some tough competition in Manchester but taking part in the Paralympic World Cup will be a new experience in itself.
"Having the opportunity to compete in a big event in my home country will be a great experience that I'm really looking forward to."
But injury has denied American amputee sprint star Marlon Shirley a chance of competing against South African rival Oscar Pistorius for the first time since the Athens Paralympics.
He is joined by Canadian wheelchair racer Chantal Petitclerc, who was also forced to withdraw through injury.
But Pistorius, a double amputee, who won gold in the T44 200m in Athens in 21.97 seconds, will compete over 100 and 200m in Manchester, defending the titles he won 12 months ago.
1-4 May: Wheelchair Basketball (Manchester Velodrome)
5 May: Track Cycling (Manchester Velodrome)
6 May: Swimming (Manchester Aquatic Centre)
7 May: Athletics (Manchester Regional Arena)
Paralympic swimming champions Sascha Kindred and Matt Walker are among the top athletes competing in the pool on Saturday.
Both recently set new world records at the British Swimming Championships with Kindred taking the 200m individual medley mark.
Dave Roberts is also in action and hopes to claim the S7 50m freestyle record back from Walker.
He told BBC Sport: "After holding it for six years, I want to get it back and I know I can do it.
"Matt and I have had a good rivalry since around 1999 and I'm looking forward to racing him again. If anyone was to take the record off me I thought it would be him."
Meanwhile, South African swimmer Natalie du Toit returns to compete at the scene of her show-stealing win in 2005.
Du Toit smashed four world records on her way to three victories at the Manchester Aquatic Centre.
Du Toit said: "I'm sure there'll be some fantastic performances in the pool again this year and hopefully I can deliver my best again."
Britain's Paralympic 1km time-trial gold medallist Aileen McGlynn will once again take on her big rival, Lindy Hou of Australia in Friday's cycling event.
At the 2005 event, McGlynn and her pilot Ellen Hunter claimed back-to-back wins against Hou and Janelle Lindsay in the tandem sprint before beating the Australians again in the 1km time trial.
GB performance coach Dave Mellor sees the event at Manchester Velodrome as a vital part of this year's plans.
He told BBC Sport: "This is an important part of our preparations for the World Championships in Switzerland later this year.
"However some of our riders will have a busy schedule with all of the events taking part in one night, rather than over a couple of days
"But we are hoping for some good performances and some world records."