In short, if they avoid a four-goal defeat they will be safely through.
Against Wales, Kyle Walker is set to start his first England game at this World Cup, as Southgate opts for minor changes for their final group game.
Group stage fixtures
All times in GMT
England 6 Iran 2 - November 21
USA 1 Wales 1: November 21
Wales 0 Iran 2: November 25
England 0 USA 0: November 25
Iran vs USA: Tuesday November 29, 7pm (GMT), 10pm local time, 2pm (ET) (Al Thumama Stadium, Doha)
Wales vs England: Tuesday November 29, 7pm (GMT), 10pm local time, 2pm (ET) (Ahmad bin Ali Stadium, Al Rayyan)
England's Group B opponents
Wales reached the World Cup finals in dramatic style via the qualifying play-offs, after beating an impassioned Ukraine side in Cardiff in June. Victory for Wales' talent-studded golden generation booked them a trip to the nation's second ever World Cup finals – their first since 1958.
This year also marked USA's return to the tournament after an absence, albeit a less protracted one. After failing to make it to Russia in 2018, USA came third in Concacaf qualifiers to secure their place in Qatar. More so than ever, team players were familiar to Premier League fans, due to the league's recent influx of American players, including Tyler Adams and Brenden Aaronson at Leeds, Antonee Robinson at Fulham, and USA captain Christian Pulisic, who plays for Chelsea.
Iran were and still are the underdogs of Group B. Although a Fifa ranking of 22 suggests they are by no means one of the weakest sides in the competition statistically, preparations were marred by infighting while head coach Dragan Skocic has been replaced by former manager Carlos Queiroz, who oversaw the team's group stage knock-out in Russia.
World Cup schedule
If England win Group B
France are favourites to win Group D, over Denmark, Tunisia and Australia, and would face the Group C runner-up out of Argentina, Saudi Arabia, Mexico or Poland to win the chance to face England in the quarter-finals, should Southgate's men make it out of the last-16 knock-out round.
If England reached the semi-finals, they could meet either Belgium or Portugal, strong contenders in Group F and H, and a potential final could see England meet Spain, Brazil, or Germany.
If England finish as runners-up in Group B
This would set up a clash between the winner of Group A, and if England were to beat Holland, they could face Argentina or Denmark in the quarter-finals.
In this scenario, should England make it to the semi-finals, their opponents might be one of either Spain, Germany, or Brazil, the cream of the crop from Groups E and G, to set up a possible final against France, Belgium, or Portugal in Lusail.
The first two quarter-finals will take place on Friday, December 9, at 3pm and 7pm, and will be played at Education City Stadium and Lusail Iconic Stadium. The remaining quarter-finals are on Saturday, December 10, at 3pm and 7pm, and will be played at Al Thumama Stadium and Al Bayt Stadium.
The semi-finals will take place on Tuesday, December 13 and Wednesday, December 14, at Lusail Iconic Stadium and Al Bayt Stadium, with both matches taking place at 7pm.
The World Cup final will take place on Sunday, December 18 at 3pm at Lusail Iconic Stadium.
Who is in the England squad?
Southgate named a 26-man squad for the tournament, including call-ups for James Maddison and Conor Gallagher.