To obtain higher medical education at the beginning of the 20th century Latvian youth mainly studied in Tartu, as there was no university in Riga. Riga had a favorable geographical position, the population increased, thus the number of patients also increased. The hospitals were well equipped, but there were relatively few doctors. In 1910, when it was planned to expand the Medical Faculty of the University of Tartu, the question arose whether it would not be expedient to transfer it to Riga. The initiative was opposed by Germans in Tartu, who feared that the Faculty of Medicine might be followed by others. The then Riga City Council, which had a relatively large number of Germans, did not agree with this idea either. The proposal was rejected by a majority.

Immediately after the founding of the Higher School of Latvia (later the University of Latvia) in 1919, the Minister of Education K. Kasparsons asked a group of Latvian doctors to attend to the establishment of the Faculty of Medicine. A subcommittee was set up on 28 August, 1919 for that purpose.  It was concluded that senior students would be able to acquire clinical knowledge in hospitals,but there was no  no premises, equipment, nor for teaching theoretical subjects for 1st and 2nd year students. Deciding on the necessity to establish FM, the subcommittee took great responsibility. It was decided that lecturers should be recruited from the midst of Latvian specialists, and only in those disciplines where there were no Latvians, specialists were invited from abroad. The core of FM was formed, and E. Zariņš was elected as a Temporary Dean. On September 11, 1919, the first official meeting of the FM Dean's Office took place. Overcoming the initial difficulties, a modern teaching and research base was created, differentiating medicine into scientific disciplines and university classes. The faculty started its activities not only with the first one, but also with several older courses, with students who came from other universities. The teaching staff was mainly recruited from graduates of the University of Tartu, University of Moscow, as well as the St. Petersburg Military Medical Academy. Some lecturers were invited from Swedish, Austrian and US universities. In 1920, the FM was granted the building of the former Orthodox seminary on Pushkin (now Kronvalda) Boulevard 9. This building was commonly referred to as the Anatomical Museum, as it first housed the Department of Anatomy. In the following years, the Departments of Physiology and Physiological Chemistry, General Pathology, Hygiene and Microbiology, as well as Pharmacology joined in the building. Rooms for the Dean's Office and Chancellery were added. Since 1928, the clinical base of the faculty has been the Riga City Hospital No. 2 (now P. Stradiņš Clinical University Hospital). Students were also trained at Riga City Hospital No. 1, Red Cross Hospital, Children's Hospital, Sarkankalns Psychiatric Hospital, City Morgue on Maskavas Street, etc. In 1920, the FM Dental Department was opened, for which the building at 9 Stabu Street was adapted.

Over the years, the clinics and departments of the ULFM were well established and worked successfully. The number of professors and their published scientific research gradually increased. Initially, a large part of the teaching staff was graduates of higher education institutions of the Russian Empire, who brought its traditions with them (strict department structure, election of professors almost for life, etc.). Curricula and the course system were taken over from Russian universities, making only small changes according to the requirements of the age - moving to 6-year studies in 1922, giving up lectures during the 6th year in 1930, discussing the subject system in the late 1930s. In the second half of the 1930s, when the old generation of professors left, a new generation of professors were elected as the heads of clinics and departments. These professors had received their medical education in Riga. 

The first twenty years included the establishment, stabilization as well as development of the FM and concluded with the change of the first generations. Among the professors of the faculty were two rectors of the University of Latvia - ophthalmologist Jānis Ruberts and internist Mārtiņš Zīle.

The time of change brought about by the Soviet occupation in 1940 also had a significant impact on the Faculty of Medicine. The Soviets disliked the model of traditional universities, and already in 1941 there were secret plans to separate the medical school from the university, as evidenced by the decision "On organizing the Medical Institute" made at the meeting of the Central Committee of the LCP on 4 June, 1941. These changes were not implemented due to lack of time.

Significant changes took place at the end of the war. The FM stopped working for a short while and lost the majority of its professors, teachers, as well as students. Some teachers were replaced, others were repressed. Several successful science schools ceased existing.

Immediately after the war, the establishment of the Riga Medical Institute was not really possible, because first the FM had to be restored. The renewal was taking place at a rapid pace, thanks to the energetic Dean, professor Pauls Stradiņš. A huge influx of students followed. The number of graduates was affected by the transition from a six-year to a five-year Soviet medical study program in 1945 and back to a six-year program in 1947.

However, at the meeting of the Central Committee of the LCP in 1946, the Faculty was criticized the most, describing the teaching staff as politically unreliable, as well as accusing the employees of insufficient qualifications. Teachers from other regions of the USSR were involved in the work of the FM. They gradually took leading positions and thus introduced the traditions and agenda of Soviet universities in Latvia.

As the diplomas obtained during the German rule were not recognized after the war, exams had to be retaken, which most of those who remained in Latvia did so immediately or after some time (even after returning from Siberia after 1960), thus graduating from the Faculty twice. It was usually a formal process, as well-known subjects had to be transferred, with the exception of Marxism and Leninism, which had been added to university curricula.

Following the example of Soviet universities, in 1949 the Department of Pharmacy, which had previously been part of the Faculty of Chemistry, was transferred to the FM.

After several unsuccessful attempts to liquidate the FM and establish an institution loyal to the Soviet regime, on 10 June, 1950, the USSR Council of Ministers issued an order establishing the Riga Medical Institute on the basis of the Faculty of Medidicne of the State University of Latvia.

From 1920 to 1950, 2058 doctors, 752 dentists, 53 pharmacists graduated from the University of Latvia; a total of 2863 graduates.

With the Latvian National Awakening and the renewal of the Latvian Medical Association in 1988, the popular professor Ilmārs Lazovskis put forward the idea of ​​the need to transform medical education. The idea of ​​FM returning to the University of Latvia became more and more real in the academic community. There was no noticeable change yet, only the Riga Medical Institute was renamed the Latvian Medical Academy (since 2002 - Rīga Stradiņš University).

The changes in higher medical education began with the escalation of internal contradictions in the Latvian Medical Academy, where free-thinking and democratically-minded teachers saw a way out of the idea of ​​renewing the FM at the University of Latvia. Disagreements with the new management of the academy became more and more unpleasant, materializing in economic threats and dismissal of teachers not because of a lack of competence but because of differing views.

Despite the risk of subsistence, Assistant Professor Uldis Vikmanis decided to unite his unjustifiably fired colleagues, finding like-minded people to work in the development of modern study programs. The first meeting of the initiative group took place on 22 October 1997. In a short time, a petition was prepared for the Rector of the University of Latvia Juris Zaķis, “On the Necessity to Renew the Faculty of Medicine at the University of Latvia”. This was followed by a conversation with the Rector during which he expressed support for the renewal of the Faculty. The principal support of the commissions of the Senate of the University of Latvia was found on 24 November, while the meeting of the Senate of the University of Latvia, important for the renewal of the FM, took place on 27 December, 1997. The Senate of the University of Latvia unanimously adopted decision No. 170 “On the Renewal of the Faculty of Medicine at the University of Latvia”. Intensive work began to prepare everything for the start of studies next autumn. By the order of the Rector of the University of Latvia on 2 February, 1998, U. Vikmanis was appointed the Temporary Dean of the Faculty.

Study programs for obtaining a medical doctor's degree were successfully prepared and approved by the Senate on 23 March, 1998. On 1 June, the FM officially began working, but on 15 July, the first 13 professors were elected to the Habilitation and Promotion Council of the Latvian Institute of Experimental and Clinical Medicine.

The FM Renewal Fund was established. The first 30 students were then admitted to the budget group. The solemn meeting of the renewal of the FM took place on 4 September, 1998 in the Aula Magna of the University of Latvia and on 7 September the studies began at the Faculty. As general education subjects (Biology, Chemistry, Physics, Foreign Languages) are acquired in the initial stage of studies, their teaching was undertaken by the relevant faculties of the University of Latvia, but FM started training in Human Anatomy. At the same time, the organizational structure of the Faculty was established. On 15 September, the Faculty Council consisting of 18 people was established, electing Prof. Māris Baltiņš as Chairman and Prof. Arnis Vīksna - as the Secretary. At the 23 December meeting of the FM Council, Prof. Uldis Vikmanis was unanimously elected as a Dean, who until then served as Interim Dean.

On 20 October, 1998, the Faculty signed the first cooperation agreement for the acquisition of clinical subjects with the Latvian Maritime Medical Center, where the Surgery Clinic of the FM was opened. Similar agreements were concluded with Riga 1st Hospital, Latvian Oncology Center and other medical institutions.

On 26  November, 1998, the Center for Social Pediatrics of the FM was opened in collaboration with Professor Theodor Hellbrügge of Munich. Extensive co-operation took place with partners both in Latvia and abroad. The response of foreign Latvian organizations in the form of various gifts should be especially noted, the graduates of the pre-war Faculty also were a great support.

In the field of research, the Faculty mainly inherited topics from the previous jobs of the teaching staff, and thus also extensive cooperation with many scientific institutions. The best confirmation of the strengthening of the Faculty was the installation and opening of the Dean's Office on 25 November, 1999 on Šarlotes iela 1. FM was located there until September 2013, when the Dean's Office was moved to the main building of the University of Latvia. Later, the most significant medical institutions in Riga - Pauls Stradiņš Clinical University Hospital, Riga 1st Hospital, etc. - became stable study bases of the Faculty in terms of students' clinical training. With the stabilization and inclusion in the annual rhythm of work, FM was no longer the smallest faculty of the University of Latvia. Today, medical studies at the University of Latvia are traditionally among the most popular choices of applicants, there is a significant competition not only for entering the budget group, but also for obtaining a paid study place. The Faculty trains not only future doctors, but also nurses, radiographers, pharmacists and dentists.

In February 2019, FM acquired a permanent residence - now the premises for faculty administration and preclinical education are located in the House of Science of the University of Latvia, Jelgavas Street 3.