Iran goalkeeper Alireza Beiranvand was forced to leave the field after a clash of heads with his teammate Majid Hosseini just 20 minutes into the match.
Jude Bellingham got England off the mark in this World Cup with a soaring header from Luke Shaw's cross 10 minutes before the break and the game was wrapped up before half-time thanks to Bokayo Saka's fine strike and Raheem Sterling's classy volley with the outside of his foot from Harry Kane's cross.
Saka scored once again in the 62nd minute to make it 4-0.
Iran's supporters were given a moment of real delight when Mehdi Taremi pulled a goal back in the 65th minutes.
Substitute Marcus Rashford scored with his first involvement in the 71st minute.
Jack Grealish slotted home from close range after a good run and pull back by Callum Wilson in the 90th minute.
Iran did pull another back in injury time when Taremi slotted in a penalty after a John Stones foul.
Iran will play Wales and the US on November 25 and 29.