What looked like being one of the ties of the group stage instead became a rather strange encounter given the talk about the most favourable knockout route, including suggestions that finishing runners-up may be preferable.
Southgate dismissed that before seeing his team suffer their first defeat in a year, with Januzaj's superb effort six minutes into the second half securing a narrow victory which earned Belgium top spot in Group G and a last-16 tie against Japan.
The Three Lions will be hoping to win their first knockout match since 2006 in Moscow next Tuesday, when widespread changes are again on the cards after their squad players struggled against Roberto Martinez's reserves.
Belgium made nine changes and England eight for the pool decider in Kaliningrad, where the teams were booed off after a tepid first half in which Gary Cahill and Trent Alexander-Arnold both cleared off the line.
Southgate's men would have progressed as group winners through fair play had the scores remained level, but former Manchester United man Januzaj's moment of magic turned the game in Belgium's favour.
Marcus Rashford and substitute Danny Welbeck went closest to an equaliser on a night when Belgium's second ever win in this fixture left England plotting their route to Moscow.
If England are to overcome Colombia next week, they will need to play far better than they did at the compact Kaliningrad Stadium.
In truth, neither side impressed once an open start tapered off.
Jamie Vardy saw an early driven cross unconvincingly stopped by Thibaut Courtois, before Jordan Pickford denied Youri Tielemans from distance.
It was a Hollywood save but at least it was a stop, whereas minutes later Cahill had to come to the Everton goalkeeper's rescue to clear off the line after Michy Batshuayi's attempt somehow squirmed through.
Cahill and Vardy headed wide for England as the tempo slowed, with Alexander-Arnold, making his second England appearance, hacking clear after Marouane Fellaini got a shot away that looked bound for the bottom corner.
There was not much else to talk about in a meek half that saw Belgium race ahead in the ill-discipline stakes, with Tielemans and Leander Dendoncker booked for fouls on Danny Rose.
And while Alexander-Arnold went close with a cross-shot and Ruben Loftus-Cheek headed wide, the locals had become restless.
Having whistled prolonged spells of purposeless Belgian possession, it was little surprise to hear the half-time whistle greeted by boos.
John Stones, pictured with a bandaged calf, was replaced by Harry Maguire for the second period, which was six minutes old when the neutrals finally had something to shout about.
Many English fans will not have seen Januzaj since slipping out of the Premier League as a Sunderland player, but he showed a flash of the outstanding skill that had once excited Manchester United supporters by following superb quick feet with a fine finish.
It saw Belgium take control of a match that England struggled to come back into.
Questions over Vardy and Rashford's chemistry grew as they toiled, only once truly connecting well as the Leicester striker put the United forward through.
Courtois' slight touch helped take Rashford's shot wide and substitute Welbeck, the last outfield player to represent England at this World Cup, was denied by a Fellaini block.
That was the last real England threat as Belgium ended the night on top.
Late change Dries Mertens' first-time strike forced a great save from Pickford and Fellaini smashed into the side-netting in stoppage time.