Brendan Rodgers' side begins the campaign without Luis Suarez, who continues his 10-match ban, while new Potters boss Mark Hughes begins his reign over the American-laden side.
The Merseyside club finished a disappointing seventh last season, but lost just three games in the second half of their Premier League campaign and will hope to extend that form into 2013-14.
Stoke has failed to register a single Premier League goal in five visits to Anfield but has taken points on three occasions courtesy of 0-0 draws, including in both of the last two seasons.
The challenge the Potters pose to Rodgers' men this time around will be vastly different, however, following the dismissal of former boss Tony Pulis and arrival of Mark Hughes in his stead. The Welshman has allowed several stalwarts of the Pulis era to leave, with Rory Delap, Matthew Upson and Dean Whitehead all released upon the expiration of their contracts.
And he has put his own stamp on the squad with the summer acquisitions of U.S. forward Juan Agudelo (who will join the club Jan. 1), Marc Muniesa and Erik Pieters.
Liverpool is also likely to field an unfamiliar lineup, having brought in Simon Mignolet, Iago Aspas, Kolo Toure and Luis Alberto during the transfer window, while Jamie Carragher's absence is sure to be felt following his retirement.
The hosts will be without Luis Suarez, as the striker serves the remainder of his 10-match ban for biting Branislav Ivanovic, and they have doubts over the fitness of Daniel Agger and Martin Skrtel ahead of the game, although Rodgers expects the central defensive duo to be available.
Daniel Sturridge is likely to command a starting berth having proven his fitness with a brief friendly appearance against Celtic and a behind-closed-doors outing against Newcastle earlier this week. Rodgers has no doubts that the forward can deliver following the ankle injury he sustained while on international duty with England in May.
"He's worked tirelessly with the medical group. As a team, they've got him back. He's not 100 percent fit yet, but for me Daniel Sturridge is a player that even if he's 70 or 80 percent fit, he'll be right up there as one of the top strikers," Rodgers said.
By contrast, Stoke has just one injury worry ahead of their opening fixture, with American winger Brek Shea sidelined by a leg injury suffered in a friendly against the Philadelphia Union. Compatriots Geoff Cameron and Maurice Edu should be available for selection by Hughes.