It was commissioned by Mihrimah Sultan, the daughter of Suleiman the Magnificent, and designed by the chief imperial architect Mimar Sinan.

It was designed by Mimar Sinan and although there is no foundation inscription the evidence from surviving manuscripts suggests that building work started in 1563 and was completed by 1570.

A portico divided into individual cells forming a medrese (Islamic school) surrounds the mosque's large courtyard.

Much of the surface area of the walls is made up of windows, making the mosque one of the lightest of any of Sinan's works.

Mihrimah Sultana herself is buried at the Süleymaniye Mosque, but a ruined türbe behind this mosque houses the graves of her son-in-law, the Grand Vizier Semiz Ali Pasha, her daughter Ayşe Hümaşah Sultan, her grandsons Mehmed Bey, Şehid Mustafa Pasha and Osman Bey and many other members of her family.