Although they trail Group H leaders Montenegro by two points, qualification remains in England's hands as they have a game in hand.
After tackling Moldova, they face a testing trip to Ukraine on Tuesday before back-to-back home games against Montenegro and Poland in October.
Roy Hodgson's side were held to a 1-1 draw away to Montenegro in their last qualifying game in March - a disappointing result, given their dominance of the first half in Podgorica - and their subsequent friendly displays have been mixed.
They were held to a 1-1 draw by the Republic of Ireland in May and drew 2-2 with Brazil in the inaugural match at the revamped Maracana in Rio de Janeiro in June.
Their last outing, meanwhile, was a topsy-turvy home game with old rivals Scotland, who twice went in front, only to lose 3-2 after Southampton striker Rickie Lambert scored the winning goal moments after coming on for his England debut.
In their last 10 matches, England have only kept clean sheets against Group H whipping boys San Marino, and although they crushed Moldova 5-0 in last September's reverse fixture, the eastern European side have improved significantly since then.
Montenegro needed a 78th-minute goal from Mirko Vucinic to overcome Moldova in March, while Ion Caras's side only lost 2-1 to Ukraine before holding Poland to a creditable 1-1 draw in Chisinau in June.
England manager Hodgson says he will not take Moldova lightly, although he is confident that his players' thoughts are not already turning towards the showdown with third-place Ukraine in Kiev next week.
"They lost in the last minute against Montenegro and to a very fortunate goal, otherwise they'd have had an even better points tally," he said.
"I don't think I will need to caution the players or get them to guard against complacency because as yet, I haven't seen any signs of that in the games we've played. If I did think that any complacency was creeping in, I'd be very quick to move in and quash it."
Hodgson's preparations were disturbed by a batch of withdrawals from his squad. Defenders Phil Jones and Glen Johnson both pulled out after sustaining injuries in Liverpool's 1-0 win over Manchester United in the Premier League on Sunday, while Daniel Sturridge, who scored Liverpool's winning goal, is doubtful with a thigh injury.
With Wayne Rooney unavailable after requiring stitches in a deep facial gash and Tottenham Hotspur striker Jermain Defoe short of sharpness, Hodgson must choose either Lambert or Rooney's United team-mate Danny Welbeck to lead the line.
Everton teenager Ross Barkley and Spurs winger Andros Townsend will both hope to make their international debuts, having been called up for the first time.
There has been much focus on the paucity of English talent in the Premier League in the build-up to the game, after only 33 per cent of the players who started games on the opening weekend of the season were qualified to play for England.
New Football Association chairman Greg Dyke called for profound changes to the national game in a speech on Wednesday, but despite a long legacy of under-achievement at international level, the current England side know that they are almost within sight of a prized place in Brazil.
"It would be a career highlight for me to play in the World Cup, so I am really hungry to get there. I am desperate to get there and I hope we can," said centre-back Gary Cahill of Chelsea. This is the crunch time. We have to get results."