Uesugi Tomooki served as a bushō and daimyō during the Sengoku period.  Tomooki was the head of the Ōgigayatsu-Uesugi family.

In 1488, Tomooki was born as the son of Uesgui Tomomasa.  Later, he was adopted by his uncle, Uesugi Tomoyoshi.

In 1505, his adoptive father, Tomoyoshi, was defeated in a conflict with the Yamanouchi-Uesugi family and forced into retirement.  As a result, Tomooki inherited the headship of the Ōgigayatsu-Uesugi family although Tomoyoshi remained the de facto head by continuing to exercise his authority from behind the scenes.

In 1518, after the death of Tomoyoshi, Tomooki acquired the power of his position but, in the later years of Tomoyoshi’s life, a natural son named Uesugi Fujiōmaru was born and, while on the verge of death, Tomoyoshi stated in his will that headship of the clan be transferred to Fujiōmaru after he matured.  This relegated Tomooki to the role of a guardian of Fujiōmaru.

Initially, Tomooki aligned with Ashikaga Yoshiaki (the Oyumi kubō) and Hōjō Ujitsuna (a rising daimyō) to oppose the Yamanouchi-Uesugi family.  From around 1523, however, he distanced himself from Ujitsuna and moved in the direction of a settlement with the Yamanouchi-Uesugi family.

In the first month of 1524, Tomooki reconciled with Uesugi Norifusa of the Yamanouchi-Uesugi.  At the same time, Ōta Suketaka colluded with Ujitsuna so Tomooki was attacked by the Hōjō army at Edo Castle.  Tomooki said “If you take on the enemy while remaining in place, it is the same as using no force.” 

On 1/13 of Daiei 4 (1524), in the Battle of Takanawahara, Tomooki led a large army to intercept the Hōjō forces at Takanawahara, resulting in a violent clash.  During this battle, the two armies engaged in mortal combat against one another, pressing forward and then retreating over the course of seven or eight times.  In the end, the Hōjō succeeded in pushing back the Uesugi forces who retreated to Edo Castle.  Ujitsuna, however, did not yield, descending upon the castle in a ferocious assault.  Unable to hold Edo Castle, Tomooki fled to Kawagoe Castle. Next, he sought refuge (via Matsuyama Castle in the Yokomi District of Musashi) in Fujita in the environs of Hachigata Castle, resulting in a victory for the Hōjō army. 

In the second month, Ōta Sukeyori from the same family as Suketaka colluded with Ujitsuna and took away Iwatsuki Castle.  In the same month, he reverted to serve Tomooki so remained in Iwatsuki Castle.

In the second month of 1525, after incurring a counterattack from Hōjō Ujitsuna, Sukeyori lost Iwatsuki Castle and temporarily withdrew to Ishido Castle.  As a result, Tomooki sought to forge an alliance with Uesugi Norifusa (his archenemy of the Yamanouchi-Uesugi family), Takeda Nobutora (a sengoku daimyō and the military governor of Kai who fought against the Hōjō in the Tsuru District of Kai), and Mariyatsu Jokan (a sengoku daimyō from Kazusa Province).  In the eighth month of 1525, at the Battle of Shirakobara, he defeated the Hōjō forces and, in the sixth month of 1526, reclaimed Warabi Castle in the Adachi District of Musashi.

In the sixth month of 1530, at the Battle of Ozawagahara, Tomooki was defeated by Hōjō Ujiyasu, the lineal heir of Ujitsuna.  In the ninth month, owing to an attack by Ōta Sukeyori, he recovered Iwatsuki Castle.  In 1532, he murdered Fujiōmaru (at the age of fifteen) and appointed his own son, Uesugi Tomosada, as his formal successor.

In 1533, Tomooki had his daughter become the formal wife of Katsuchiyo (Harunobu and, later, Shingen), the lineal heir of Takeda Nobutora.  The Yamanouchi-Uesugi and Takeda clans joined forces to attack Hōjō Ujitsuna.  In 1533 and 1535, the forces invaded Sagami Province, continuing to pose a military threat to the Hōjō.  Ultimately, Tomooki could not recover Edo Castle.  On 4/27 of Tenbun 6 (1537), he died of illness at Kawagoe Castle.  He was fifty years old.  Tomooki was succeeded by his eldest son, Uesugi Tomosada.