Steven Gerrard broke the deadlock with a low, powerful strike in the 12th minute and, from then on, the hosts looked completely in control, meeting the expectations of a less-than-full Wembley.
Rickie Lambert, making his first international start, continued his 100 per cent scoring record at international level with a simple header midway through the first half before turning provider twice for Danny Welbeck. The Manchester United youngster sped through a bewildered defence just before half-time and again finished coolly shortly afterwards.
The result was significant for England, who moved to the top of Group H on goal difference.
|By Wayne Veysey at Wembley
"A stroll in a half-empty park for England as they notch up an ultra comfortable three World Cup qualifying points.
"The swagger of the first half was followed by the solidity of the second as Roy Hodgson's team shut up shop, passed the ball around neatly and ensured there were no dramas.
"Shout-outs to Rickie Lambert, Danny Welbeck and Steven Gerrard, who were all very good on the night. We all know that Ukraine will provide a far sterner test of England's qualification credentials on Tuesday but this was a job well done."
Ukraine are snapping at both of their heels on 14 points from seven games after thrashing San Marino 9-0, and with just one side automatically qualifying for next year's tournament in Brazil, the stakes will be high in the remainder of the group stages.
Chelsea pair Frank Lampard and Ashley Cole returned to Hodgson's starting line-up for England, while Lambert was involved from the start after scoring the winner on debut against Scotland last month.
Wayne Rooney was the headline exclusion for the hosts, with the Manchester United forward still suffering from a head injury, while Leighton Baines and Tom Cleverley dropped to the bench.
Moldova, who made four changes themselves, were quickly on the back foot as winger Theo Walcott won England a corner inside the first 90 seconds.
Lambert headed the chance over, while he thrashed an effort wide shortly after, as England started brightly, and they soon had the lead.
The goal was created down the left, as Cole and Welbeck combined nicely, before Lampard laid off for Gerrard.
And the Liverpool star beat Moldova goalkeeper Stanislav Namasco with a fizzing strike from distance that went in off the inside of the post.
Walcott had a goal ruled out for offside in the aftermath, while Jack Wilshere and Lampard tested Namasco in a two-minute spell that ended with a second goal for the hosts.
Walcott and Welbeck had further opportunities, while a neat Moldova move saw Sergiu Gheorghiev shoot well wide under pressure from Phil Jagielka.
England sealed their victory on the stroke of half-time, though, as Welbeck, who was booked for ignoring an offside flag – which will rule him out of Tuesday's qualifier in Ukraine – responded within a minute with a goal.
Lambert supplied Welbeck with an inch-perfect cross and the Manchester United forward took a touch beyond the hapless Namasco and tapped in to give his country a 3-0 lead at the break.
It took just five minutes in the second half for England to extend their lead, as Lambert and Welbeck combined to superb effect again.
Lambert drifted out to the left to win the ball and split the defence with a neat ball, and Welbeck did the rest, dinking over the onrushing Namasco to wrap up the result.