Early on, during his life in the USA he was active in the Muslim communities where he lived. He published few Islamic newsletters and publications. He was still attached to the teachings of Islam (Submission) as he learned it from his father as well as the Sufi teachings he was brought up with. He went back to Egypt to work for few years after finishing his PhD before settling in the USA with his wife and two children. He always maintained his Islamic religious activities and appreciated by many who got to know him closely and even adopted his name, e.g. Ahmad Rashad, the former Minnesota Vikings wide receiver/sportscaster.

After many years in the USA and after reading different English translations of the Quran, he was not happy with any single one, specially that his mother tongue was Arabic, the original language of the Quran..All these translations had some violation of some of the basic teachings of the Quran. None of those who translated the Quran spoke Arabic as his mother tongue. Dr. Khalifa was also met with a challenge from his children, while studying Quran with them. They asked him about the meaning of the letters at the beginning of Sura 2 in the Quran, i.e., A,L, M. He did not have an immediate answer for them and did not find a good answer with all the Muslim scholars he asked. He started searching the Islamic text books and references, but he never was satisfied with any of the explanations. The closest explanation he could accept was that these letters represent the miracle of the Quran .
Since his job at that time required contact with the computer he was inspired into using the computer to study the Quran and its mysterious letters (initials) at the beginning of the chapters of the Quran. He decided to put all the Arabic Quran in the Computer and specifically study these initials.
He also decided to begin his own translation of the Quran.With his mother tongue being Arabic, he began to translate the Arabic Quran into, the best available to date, English translation of the Quran. None of his predecessors, for whom he read translations, actually spoke the language of the Quran, i.e., Arabic.

Dr. Khalifa's study of the Quran with the computer, the first of its kind then, resulted in the discovery of one of the greatest miracles of the Quran, as God described it in 74:35. This miracle is based on number 19, mentioned in sura 74. MATHEMATICAL MIRACLE OF THE QURAN . He published the results in several books, magazines and newspapers, and gave many lectures in many countries of the Muslim world. The Muslim scholars and governments cheered him and treated him like a hero and supported the new discoveries in the Quran.
The momentous discovery that "19" is the common denominator of the Mathematical Miracle of the Quran became a reality in January, 1974. This was coinciding with Zul-Hijjah 1393 A.H. The Quran was revealed in 13 B.H. (Before Hijrah). This makes the number of years from the revelation of the Quran to the discovery of its miracle (in 1974), 1393+13=1406 years. It was more than interesting to notice that 1406 = 19 X 74. The only time number 19 was mentioned in the Quran is in sura 74. The correlation between 19X74 lunar years and 1974 solar years could not escape notice, especially with number 19 mentioned only in sura 74.