Welbeck finished off passes from Rickie Lambert - who scored England's second goal with a close-range header on 27 minutes - courtesy of two fine finishes either side of half-time. Captain Steven Gerrard had netted the opening goal with a classy finish from distance.
But there was no hiding the disappointment etched on the face of the Manchester United striker Welbeck, who was controversially booked for booting the ball away seconds after an offside flag went up against him.
Having being booked earlier in the campaign, Welbeck misses the trip to Kiev on Tuesday with England now top of Group H on goal difference from Montenegro after their closest rivals drew 1-1 with Poland in Warsaw earlier in the evening.
England will remain top of the section with two games remaining if they avoid defeat in the Ukraine, but you could understand the frustration of Welbeck and Hodgson, who approached an official on the sidelines to complain about Welbeck's booking with England leading 2-0 and completely in command against a visiting side utterly devoid of quality or ideas.
MAN OF THE MATCH
Steven Gerrard (England) - Superb performance from the England captain. Fine goal, and just oozed class in knocking the ball around with such ease.
PRE-MATCH: TRIO OUT, LAMBERT STARTS - Wayne Rooney, Phil Jones and Glen Johnson had to withdraw from the squad to face Moldova and Ukraine with respective head and ankle injuries. Daniel Sturridge will miss the Moldova game, but will have his thigh injury assessed ahead of next Tuesday’s clash with Ukraine as will defender Steven Caulker. Sturridge will be replaced by Southampton star Rickie Lambert, while Arsenal’s Jack Wilshere featured in spite of a bout of stomach cramps last week.
12' GERRARD STRIKES: Steven Gerrard thrashes the shot low and hard into the net from 25 yards. Brilliant finish from the Lampard pass. England lead 1-0.
27' LAMBERT POUNCES: Rickie Lambert heads into the empty net after goalkeeper Stanislav Namasco made a complete mess of saving Theo Walcott's shot. England lead 2-0.
43' WELBECK ANGUISH: Danny Welbeck harshly booked for kicking the ball away after the offside flag went up. That means he is out of the trip to Ukraine on Tuesday. Roy Hodgson is furious.
44' WELBECK RECOVERY: Welbeck knocks the ball into the gaping net with Namasco all over the place again as he tried to come off his line. England lead 3-0 with Lambert playing provider.
50' MORE WELBECK CLASS: Rickie Lambert pokes the ball into the path of Welbeck, who lifts the chip over Namasco. A 4-0 lead now for England.
59' BARKLEY DEBUT: Ross Barkley was eligible to play for Nigeria before this evening, but not after tonight. Good decision by Hodgson to blood him here as he takes over from Jack Wilshere.
Rickie Lambert has scored two goals and assisted two in just 94 minutes of action for England. Excluding penalty shootouts, England are unbeaten in 19 competitive internationals - W11 D8.
Danny Welbeck has scored six goals in his last seven appearances for England.
Danny Welbeck has scored with seven of his eight shots on target for England.
Steven Gerrard's opening goal ended a run of 18 appearances for the captain without scoring for England.
TALKING POINT - How will England fare in Ukraine without Welbeck? Difficult to say with any degree of certainty. Lambert is in fine form, but you have to remember who he scored against: a tiring Scotland defence and a Moldova side who would struggle in League Two. Lambert is likely to be given the nod, but Roy Hodgson must hope Daniel Sturridge is fit enough to give him options before making his final starting choice in Ukraine.
ENGLAND: Hart 6, Walker 7, Cole 7, Gerrard 9, Cahill 6, Jagielka 7, Walcott 7, Lampard 8, Welbeck 8, Wilshere 7, Lambert 8..subs: Baines 6, Milner 6, Barkley 7
MOLDOVA: Namasco 3, Armas 4, Golovatenco 4, Epureanu 4, Ionita 4, Antoniuc 4, Dedov 4, Georghiev 4, Bulgaru 4, Bordian 4, Sidorenco 4..subs: Pascenco 4, Onica 4, Suvorov 4
THE MATCH IN A TWEET