Iran had a rough start to the match after goalkeeper Alireza Beiranvand clashed with a fellow teammate and suffered a concussion, which also delayed the match over 10 minutes.
19-year-old Jude Bellingham scored his very first international goal for England, opening the scoresheet for the Three Lions.
Bukayo Saka and Raheem Sterling quickly slotted the ball into the back of the net, making it 3-0 for England by the end of the first half.
In the second half, Bukayo Saka struck again in the 65th minute before getting substituted by Marcus Rashford.
Mehdi Taremi scored a consolation goal for Iran before new substitute Rashford made it 5-1 for England.
Jack Grealish made it six for England. Taremi got a late penalty to score Iran's second goal, but they lost to England 6-2 in their opening match of the FIFA World Cup 2022.