The Three Lions will be aiming for a confidence-boosting victory despite missing a number of key players through injury, with a daunting trip to face Ukraine the following week.
Roy Hodgson's men welcome Moldova to Wembley on Friday and are expected to record a resounding victory against the minnows.
England is unbeaten in its last six matches but is still in danger of missing next year's World Cup in Brazil.
The team sits second in Group H, two points behind Montenegro with a game in hand, while Ukraine is snapping at its heels in third, just one point back.
With the side that finishes first automatically qualifying, and the second being sent into the playoffs, Tuesday's qualifier in Kiev is particularly important.
Hodgson has selected a typically strong squad, with captain Steven Gerrard set to lead the team alongside the likes of goalkeeper Joe Hart and attacker Theo Walcott.
England does have a series of injury problems though, with Wayne Rooney (cut head) withdrawing from the squad, along with Liverpool's Glen Johnson and Manchester United's Phil Jones.
In-form striker Daniel Sturridge is also in the squad but is in doubt due to groin pain. Sturridge has scored five goals in his four matches for Liverpool this season.
Arsenal's Jack Wilshere is expected to be fit despite following stomach cramps last week, while Cardiff defender Steven Caulker could win his second cap after being called up as cover.
Moldova - ranked joint-123rd in the world, more than 100 places below England - will enter the match on the back of a three-match unbeaten run.
An excellent 1-1 home draw to Poland in Group H was followed by a 2-1 friendly win over Kyrgyzstan.
The team also drew 1-1 at home to Andorra last month in another friendly thanks to Alexandru Dedov's equalizer.
Moldova is expected to line up with a 4-5-1 formation and play for a point, but England should have too much quality.
The two sides last met in last September's reverse fixture, with England winning 5-0 in Chisinau.
Frank Lampard scored a double in that fixture, while Jermain Defoe, James Milner and Leighton Baines also netted.
England has won all three meetings between the two sides, with their last clash at Wembley ending in a 4-0 win to England in September 1997.