Reigning champion Jonny Clayton will be defending the title he claimed for the first time 12 months ago, which he sealed with victory over 2020 champion Gerwyn Price - the top seed at this year's event.
World Champion Peter Wright and five-time World Grand Prix winner Michael van Gerwen will also be among the eight seeds in the 32-player field, which includes three debutants this year.
The 25th staging of the prestigious tournament will feature seven sessions of action from October 3-9, as players compete for the coveted title and a record £600,000 in prize money.
The first round will see 16 matches take place across the opening two nights, as Clayton begins the defence of his title with a blockbuster tussle against 2020 runner-up Dirk van Duijvenbode on Monday.
"There are not many people that have defended the World Grand Prix and I'd love to join that list, so fingers crossed it's going to happen again," said Clayton, who is 11/1 to retain his crown with BoyleSports.
"The double-in double-out format is challenging, but it separates the men from the boys.
"I've had an up and down season, but hopefully things are starting to fall into place.
"I would love to break into the world's top five by the end of the year, and the only way I can do that is by concentrating hard on the ranking events at the back end of the season."
- First Rounds - Best of 3 sets
- Second Round - Best of 5 sets
- Quarter-Finals - Best of 5 sets
- Semi-Finals - Best of 7 sets
- Final - Best of 9 sets
Monday's stellar opening night features a host of thrilling ties in the bottom half of the draw, including a repeat of the 2016 final between third seed Van Gerwen and Gary Anderson.
Wright - who missed August's World Series treble-header to undergo gallbladder surgery - will also headline Monday's action, as the 2018 runner-up kicks off his bid for a maiden World Grand Prix crown against Kim Huybrechts.
"The World Grand Prix is definitely on my list. I have been practising for this tournament straight after my surgery, so I'm looking forward to it," said the Scot, a winner at last month's International Darts Open.
"The short format is tough but it's a leveller. You've got to be on it or you're out. If I can get past the first round, I'll be dangerous.
"Kim is playing well at the moment. He's in a good place and he's beaten me quite a few times recently, but this is double-start so it's a different playing field. If I hit my doubles, I'll win."
- Winner - £130,000
- Runner-Up - £60,000
- Semi-Finalists - £30,000
- Quarter-Finalists - £20,000
- Second Round Losers - £12,500
- First Round Losers - £7,500
- Total - £600,000
Sixth seed Jose De Sousa will play 2010 runner-up Adrian Lewis in another tasty tie, while newly crowned Belgian Darts Open winner Dave Chisnall will look to maintain his fine form when he faces Belgian number one Dimitri Van den Bergh.
"It's been a tough rollercoaster over the last two years. At the beginning of last year when I lost my Mum, I thought I might never win another tournament," admitted Chisnall, a World Grand Prix runner-up in 2013 and 2019.
"I normally have a good run in this tournament. I've been in a few finals, a few semi-finals. I cannot wait for it now. I'm still not 100% at my best yet, but when I do get there, they will be chasing me.
"I had an absolutely terrible year last year but I am coming back, and I see more trophies in my cabinet."
Elsewhere, 2011 runner-up Brendan Dolan takes on Stephen Bunting, 2019 semi-finalist Chris Dobey meets an in-form Luke Humphries, with Callan Rydz and Krzysztof Ratajski opening this year's tournament.
- (1) Gerwyn Price v Martin Schindler, Joe Cullen v Damon Heta
- (8) Rob Cross v Daryl Gurney, Madars Razma v Ryan Searle
- (4) Michael Smith v Nathan Aspinall, Danny Noppert v Gabriel Clemens
- (5) James Wade v Martin Lukeman, Ross Smith v Andrew Gilding
- (2) Peter Wright v Kim Huybrechts, Callan Rydz v Krzysztof Ratajski
- (7) Jonny Clayton v Dirk van Duijvenbode, Dimitri Van den Bergh v Dave Chisnall
- (3) Michael van Gerwen v Gary Anderson, Brendan Dolan v Stephen Bunting
- (6) Jose de Sousa v Adrian Lewis, Chris Dobey v Luke Humphries
World number one Price enters the fray as the first round draws to a close on Tuesday, and the Welshman faces Martin Schindler in a repeat of their showdown at July's World Matchplay.
Price followed up his victory in August's New Zealand Darts Masters by scooping his second World Series Finals title in Amsterdam a fortnight ago, and the 2021 World Champion heads to Leicester full of confidence.
"It is always nice to win. It doesn't matter if it's the World Series or ranking events - it fills you with confidence," insisted Price, the current 4/1 tournament favourite.
"If I can start off like I have in previous years, there is no reason why I can't go and win this title again.
"I know I'm playing well. I have got a lot more in the tank, but things are going in the right direction at the right time of year."
Schedule of Play
- Monday October 3 - 8x First Round matches
- Tuesday October 4 - 8x First Round matches
- Wednesday October 5 - 4x Second Round
- Thursday October 6 - 4x Second Round
- Friday October 7 - Quarter-Finals
- Saturday October 8 - Semi-Finals
- Sunday October 9 - Final
Two-time winner James Wade locks horns with debutant Martin Lukeman on Monday, with 2017 champion Daryl Gurney pitted against eighth seed Rob Cross.
Fourth seed Michael Smith and Nathan Aspinall collide in another mouth-watering clash, with UK Open champion Danny Noppert up against Gabriel Clemens, while Masters winner Joe Cullen renews his rivalry with Australia's World Cup winner Damon Heta.
Ryan Searle - a quarter-finalist in 2021 - kicks off Tuesday's action against Latvian debutant Madars Razma, before Ross Smith plays last weekend's Belgian Darts Open runner-up Andrew Gilding.
The tournament will be broadcast live on Sky Sports in the UK, through the PDC's worldwide broadcast partners including DAZN and Viaplay, and on PDCTV (excluding UK, Germany, Austria & Switzerland based subscribers).