Round Two will also be played at a solitary venue - St Helens' Totally Wicked Stadium - before each side returns home ahead of Round Three.
Here are our predictions ahead of this week's matches.
Wigan Warriors vs Wakefield Trinity
The first match of the round takes place on Thursday evening, when the Wigan Warriors take on the Wakefield Trinity.
Wigan overturned an 18-0 deficit to see off a spirited Leigh Centurions in Round One, though the result was overshadowed by a hamstring injury to summer signing Jai Field, with the Aussie half-back set for a five month spell on the sidelines.
Trinity fell to a 28-22 to defeat to local rivals Leeds Rhinos in their first competitive outing of 2021, though there were plenty of positives for Chris Chester to take from the game, none more so then the try scoring exploits of high-flying winger Tom Johnstone.
We're expecting a tight one here, though the return of Jackson Hastings should help Wigan to a narrow victory.
VAVEL Predicts - Wigan by 6.
Hull KR vs St Helens
The second game taking place on Thursday sees Hull KR take on reigning champions, St Helens.
The Saints got off to a flier in Round One, as they cruised past the Salford Red Devils, whilst the Rovers suffered Golden Point heartbreak after a remarkable second-half comeback against the Catalans Dragons.
The home field advantage should be a huge boost for the Saints, who will be looking to back up their big win against Salford ahead of a tricky run of fixtures.
We can't see past a St Helens victory here.
VAVEL Predicts - St Helens by 20
Warrington Wolves vs Leigh Centurions
Looking ahead to Saturday now, when the Warrington Wolves take on the Leigh Centurions.
The Centurions shone in the first half of their Round One defeat to the Wigan Warriors, though their lack of fitness got the better of them in the second-half as the Warriors left Leeds with the two points.
Warrington also got off to a losing start, as they disappointed in defeat to the Castleford Tigers.
The Wolves will be looking to bounce back in this one. If the Centurions can put in a similar performance to Round One then they could run them close, but we can't see it.
VAVEL Predicts - Warrington by 14.
Leeds Rhinos vs Castleford Tigers
The match of the round takes place on Saturday evening, when the Leeds Rhinos take on the Castleford Tigers.
Both sides were victorious in their opening fixture, though it was the Castleford Tigers who drew the most plaudits, as off-season acquisition Niall Evalds lead the Yorkshire outfit to victory over Warrington.
This has all the makings of a classic, though Leeds' leaky defence will need to sure up if they are going to stop the attacking exploits of the Tigers.
We're taking Castleford in a close one.
VAVEL Predicts - Castleford by 6.
Hull FC vs Salford Red Devils
Saturday afternoon sees Brett Hodgson's Hull FC come up against Richard Marshall's Salford Red Devils.
Both sides have undergone a pre season makeover, though its FC who came out the better in Round One, as they breezed to victory over the Huddersfield Giants.
Salford were better than the scoreline suggested against St Helens, with the performance of off-season signing Elijah Taylor a particular bright point.
This could be closer than many are expecting, though FC should have too much quality for the Devils.
VAVEL Predicts - Hull FC by 10.
Huddersfield Giants vs Catalans Dragons
The final fixture of the round sees the Huddersfield Giants take on the Catalans Dragons.
The Giants were arguably the most disappointing side in Round One, with many expecting big things from Ian Watson's side this season.
The Dragons surrendered a 28-4 lead over Hull KR yet came away with the points courtesy of James Maloney's Golden Point drop goal.
This could be a high scoring affair, though the return of Aiden Sezer could be enough for the Giants to edge it.
VAVEL Predicts - Huddersfield by 8.