Youssef was born in 1948 in Assuit, Egypt. He was raised in a Christian home, but often tells of how he was saved in 1964 at the age of 16. During the Six-Day War Youssef left Egypt for Lebanon where, after six months, he visited the Australian embassy and was granted a temporary visa to that country. While in Australia, Youssef studied at Moore Theological College in Sydney, was ordained as a minister, and met his wife, Elizabeth.

The Youssefs came to America in 1977, and in 1978 Michael Youssef received a master's degree in theology at Fuller Theological Seminary in California. He later earned a doctorate in social anthropology from Emory University in Atlanta, Georgia. Youssef worked for nearly 10 years with the Haggai Institute, traveling around the world, teaching courses in evangelism and church leadership to church leaders, eventually rising to the position of managing director at the age of 31. Youssef became a U.S. citizen in 1984 and currently resides in Atlanta.

He founded the Church of the Apostles in 1987 proclaiming the mission to "reach the lost and equip the saints." From its initial size of around 40 members, the congregation has since grown to over 3,000 people and was the launching pad for Leading the Way...an international ministry which broadcasts via radio and television to over 200 countries and in over 20 languages.

In November 2009, Youssef signed an ecumenical statement known as the Manhattan Declaration calling on evangelicals, Catholics and Orthodox not to comply with rules and laws permitting abortion, same-sex marriage and other matters that go against their religious consciences.