Mohammed bin Salman Al Khalifa was the youngest of three sons of the hakim of Bahrain, Salman bin Hamad Al Khalifa. His eldest brother, Isa bin Salman Al Khalifa, succeeded as hakim, and his other late brother, Khalifa bin Salman Al Khalifa, was the prime minister. Mohammed was uncle to the reigning king, Hamad bin Isa Al Khalifa.