Mehmet Sami was born in Istanbul and first studied art under Osman Nuri Paşa at Kuleli Military High School. In 1896 he entered the Military Academy, where he was taught art by Hoca Ali Rıza. In 1899 he was appointed art teacher at the Military Veterinary High School in Eyüp. He began his studies at the School of Fine Arts in 1900, graduating with a first class degree. In 1910 he went to Paris to study with the assistance of Commander-in-Chief Mahmud Şevket Paşa. In Paris he studied at the Julian Academy, where he attended the studio of Jean-Paul Laurens. He returned to Turkey in 1912 and fought in the Balkan War with his friend Mehmet Ali Laga. In 1917 he worked at the Şişli Studio established by the Ottoman Minister of War Enver Paşa. Meanwhile he was among the founders of the Ottoman Society of Painters. He completed the first volume of his book Ressamlarımız (Our Painters) in 1940, but was unable to write the second volume.
The Ottoman Society of Painters was established in 1909 by artists including Ruhi Arel, Sami Yetik, Şevket Dağ, Hikmet Onat and İbrahim Çallı, under the patronage of the last Ottoman caliph the Prince Abdülmecid Efendi (1868-1944), who was himself a painter. The society was an independent body that came into being in the new liberal atmosphere following the proclamation of the Second Constitution in 1908. It was dedicated to spreading interest in art and awareness of painting as a profession in Ottoman society. Later on artists like Feyhaman Duran, Hüseyin Avni Lifij and Müfide Kadri joined the society, which was the first professional association of artists in Ottoman Turkey.
Mehmet Sami was one of the '1914 Generation' of painters. This group included the young Ottoman artists who went to Europe to study art in 1909-1910—principally at the Julian Academy in Paris—but were obliged to return home at the outbreak of the First World War and so came to be known as the 1914 Generation. They included leading painters like İbrahim Çallı, Nazmi Ziya, Avni Lifij, Feyhaman Duran, Namık İsmail and Hikmet Onat, who played an important part in the spread of such genres as landscape and still life in Turkish painting. Another striking aspect of their work is the way their paintings reflect their own impressions and personal interpretations. Owing to their pure colours and sensitivity to light, these painters are sometimes described as the Turkish Impressionists. Almost all of them were among the first Turkish teachers at the Academy of Fine Arts in Istanbul and so were active in training the next generations of Turkish artists.