Maguire sat on the Khalifa International Stadium turf just after the hour and was immediately tended to by England’s medical team.
The physios could be seen conducting a concussion test, which is protocol in such scenarios.
It was not entirely clear how Maguire suffered the injury. He was treated for several minutes before being led off the pitch.
The 29-year-old was clearly very dazed as he chatted with staff. He then exchanged words with his replacement, Eric Dier, before heading straight down the tunnel.
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The 48-cap ace hit back at critics of his World Cup inclusion with his performance. However, he could now miss England’s game with the USA on Friday after being substituted due to concussion.
Under FIFA guidelines, any player who suffers a concussion must be reassessed within 72 hours of leaving the pitch. That could leave Maguire facing a race to be ready for the second Group B clash.
That differs to the Premier League guidelines, which insist that players must not take part in sporting activity for at least six days.
England continued to cruise beyond Iran without Maguire.
They led 4-1 before his injury, with Jude Bellingham, Raheem Sterling scoring and Bukayo Saka striking a brace.
Mehdi Tahremi grabbed a goal back for the Asian side, before Maguire’s Man Utd team-mate Marcus Rashford restored the four-goal lead having only just come on as a substitute.
Jack Grealish scored a sixth goal to round off a super start to the 2022 World Cup for Gareth Southgate’s side.
Tahremi scored a late penalty for Iran after John Stones was punished for shirt-pulling.
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