The victory, earned courtesy of a Harry Kane hat-trick and Raheem Sterling strike, has seen the Three Lions move to the top of Group A on nine points ahead of their next game against Kosovo on Tuesday night.
It did not take long for the hosts to exert their dominance in terms of possession, but England goalkeeper Jordan Pickford had to make the first save of the match as he kept out a low strike from Wanderson in the fourth minute.
England's first shot of the game arrived in the 14th minute when Jordan Henderson met a high ball outside the Bulgaria box, although the Liverpool midfielder's effort was always moving wide of the post.
The Three Lions did have the ball in the back of the net in the 19th minute when Kane converted a low Sterling cross from close range, only for the linesman's flag to disallow the goal.
Kane was not to be denied, though, and opened the scoring in the 24th minute when he dispatched a low Sterling cross after a horrific piece of defending from Bulgaria, who had attempted to play out from the back.
The next big chance of the match actually came for the visitors just past the 30-minute mark, but Ivelin Popov could only head a dangerous cross into the body of Pickford from close range.
Danny Rose then delivered a dangerous cross towards Sterling down the other end, only for the Manchester City attacker to take a heavy touch which allowed the visitors to clear their lines.
England's final chance of the half came for Kane late on when the Tottenham Hotspur forward climbed highest inside the penalty box to meet a cross from Kieran Trippier, but his header was saved by the away side's stopper.
Wanderson had a golden opportunity to level the scores early in the second period after breaking into a one-on-one with Pickford, who made a smart save to keep Southgate's side ahead.
Kane stepped forward to convert into the corner of the net as Bulgaria's chances of picking up anything from their night's work took a severe blow.
The England captain then turned provider in the 55th minute as he delivered a low cross into Sterling for the City attacker to make it 3-0 with a close-range finish.
Mason Mount was introduced for his England debut in the 66th minute after impressing for Chelsea in the early stages of the 2019-20 Premier League campaign.
The home side were awarded another penalty in the 72nd minute when substitute Kristian Dimitrov felled Kane, who climbed to his feet before finding the back of the net to complete his hat-trick.
Pickford had to make a smart save to keep out a free kick from Popov as Bulgaria looked to give their fans something to cheer late on, before Rashford was denied down the other end as it finished 4-0 in London.
ENGLAND (4-3-3): Pickford; Trippier, Keane, Maguire, Rose; Henderson (Mount 66'), Rice, Barkley; Sterling (Sancho 71'), Kane (Oxlade-Chamberlain 77'), Rashford
BULGARIA (4-1-4-1): Iliev Ivanov; Popov, Bodurov (Dimitrov 65'), Bozhikov, Nedyalkov; Ivanov (Mladenov 83'), Popov, Malinov, Wanderson; Marcelinho (Despodov 67')