England play host to a Macedonia side they only managed to beat 1-0 away last month in Rooney's absence and who can be guaranteed to make life difficult again at Old Trafford.
Rooney, who also missed England's opening Group E win over Andorra due to his red card in their World Cup exit to Portugal, has not had a particularly happy start to the season for club or country.
The 20-year-old's international ban coincided with one at club level for a red-card in a pre-season tournament in Amsterdam, ruling him out of the game completely for more than three weeks.
Though he played in United's season-opening 5-1 romp against Fulham on Aug. 20, scoring twice, Rooney has yet to score since and has made nothing like his previous impact in games for Alex Ferguson's side.
However, England coach Steve McClaren has made it clear that his support for such a gifted talent is unswerving, despite the sometimes volatile temper that comes with it.
"Players have to be playing well and have to be in form but Wayne Rooney is a world-class player and can make the difference at any given moment," McClaren said last week. "He's in my team."
That team is being tweaked in all departments, with Jermain Defoe making way for Rooney, Scott Parker tipped to stand in for injured Owen Hargreaves as a defensive midfielder and fit-again Gary Neville taking over from brother Phil at right back.
Parker faces competition for the holding role from Rooney's club team mate Michael Carrick, whose unhurried passing impressed at the World Cup.
However, Parker's energetic box-to-box performances for Newcastle this season could well tip the balance, particularly in a game where England will need to harry a side who are expected to pack the final third.
Whoever is chosen will give Frank Lampard the freedom to get forward, with the midfielder's promising return to form with Chelsea coming just at the right time for his country.
Steven Gerrard will again take the right midfield slot once filled by Beckham, who is still out of the squad despite an injury to Gerrard's understudy Aaron Lennon.
Though they will be underdogs on Saturday, Macedonia will go into the game with happy memories of playing in England.
Four years ago, they ended up with a 2-2 draw after twice being in front in a Euro 2004 qualifier in Southampton, with Artim Sakiri memorably beating keeper David Seaman with a corner kick.
England: Paul Robinson; Gary Neville, John Terry, Rio Ferdinand, Ashley Cole; Steven Gerrard, Scott Parker, Frank Lampard, Stewart Downing; Wayne Rooney, Peter Crouch
Macedonia: Jane Nikoloski; Nikolce Noveski, Robert Petrov, Goce Sedloski, Igor Mitrevski, Vlade Lazarevski; Robert Popov, Velice Sumulikoski, Ilco Naumoski; Goran Maznov, Goran Pandev