Here, the PA news agency takes a look at some of the major talking points ahead of the Group B opener.
England, as well as eight other European nations, took the decision to sport a “OneLove” captain’s armband for the current season – including, for those which had qualified, at the World Cup.
However, with FIFA since launching its own equivalent and the suggestion players wearing the non-sanctioned version could face yellow cards in matches, discussions will continue between FIFA and the Football Association to find a solution.
First night nerves
Harry Kane’s stoppage-time winner saw England edge to three points in the opening game against Tunisia in Russia four years ago, having lost to Italy in their first match of the 2014 finals.
A draw against the United States in South Africa in 2010 means the Three Lions do not exactly come flying out of the traps at World Cups.
They will want to change that in a tough test against Iran – ranked 20th in the world – and lay down a marker for the tournament.
Tried and tested
Southgate’s starting line-up against Iran could feature as many as six players who were also in the line-up that lost the semi-final to Croatia in 2018.
In fact, this squad is the second-most experienced in terms of caps of any selected for a World Cup by England.
That shows the faith and loyalty that Southgate shows in his trusted players but also the collective experience that could not only bode well against Iran but across the tournament.
The heat is on
While kick-off is 19:00 local time, it is safe to say the weather in Doha in November does not quite mirror that of England at the same time of year.
London, for example, is forecast to have highs of nine degrees on Monday while the mercury will hit 27 at times in Qatar.
England have certainly been attempting to acclimatise, holding a number of their training sessions in the midday sun to minimise any surprises.
There will be plenty of England fans inside the the Khalifa International Stadium, some travelling from home and others here from places such as India or as members of the migrant workforce.
However, they are likely to be outnumbered by their Iranian counterparts, who have made a much shorter journey.
With just the Arabian Gulf separating Iran and Qatar, it is expected that Carlos Queiroz’s side will be cheered on by vociferous support and it will be up to England to silence them from the off.