Most Rev. Michael Curry agreed to become part of the event that will take place at St. George's Chapel in the Windsor Castle.
The United States Episcopal Church was born from the Scottish Episcopal Church and the Church of England - the latter being the Mother Church of the Anglican Communion.
Traditionally, sermons at royal weddings are given by senior clergy from the Church of England.
Former actress Meghan, 36, will marry into the royal family on Saturday, May 19, when she says "I do" with Harry, 33, at midday.
After the Episcopal Church voted to allow gay marriage in 2015, Archbishop Welby said the decision "will cause distress for some and have ramifications for the Anglican Communion as a whole, as well as for its ecumenical and interfaith resolutions".
He said: "I'm always nervous at weddings because it is such an important day for the couple - whoever they are".More news: 35 people sick from salmonella-contaminated eggs
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Markle was reported to have been baptized two months ago by Welby.
Michael Bruce Curry, the 27th Presiding Bishop and Primate of The Episcopal Church, has been chosen to give the address at Prince Harry and Meghan Markle's royal wedding.
Archbishop of Canterbury Justin Welby will preside over the exchange of vows whilst the Dean of Windsor will conduct the service itself. Having an American pastor at a royal wedding is a break from tradition.
Is there anything else we should know about Bishop Michael Curry?
This weekend's royal wedding will get a sermon from an American priest who's pro-marriage equality! The sermon went viral and was later turned into a book, Crazy Christians: A Call to Follow Jesus.
In 2012, Curry gained fame for his sermon in which he quoted a version of the Bible that refers to Jesus as a insane person.