Kuniyoshi was born on January 1, 1798, the son of a silk-dyer, Yanagiya Kichiyemon, originally named Yoshisaburō. Apparently he assisted his father's business as a pattern designer, and some have suggested that this experience influenced his rich use of color and textile patterns in prints. It is said that Kuniyoshi was impressed, at an early age of seven or eight, by ukiyo-e warrior prints, and by pictures of artisans and commoners (as depicted in craftsmen manuals), and it is possible these influenced his own later prints.
Yoshisaburō proved his drawing talents at age 12, quickly attracting the attention of the famous ukiyo-e print master Utagawa Toyokuni. He was officially admitted to Toyokuni's studio in 1811, and became one of his chief pupils. He remained an apprentice until 1814, at which time he was given the name "Kuniyoshi" and set out as an independent artist. During this year he produced his first published work, the illustrations for the kusazōshi gōkan Gobuji Chūshingura, a parody of the original Chūshingura story. Between 1815 and 1817 he created a number of book illustrations for yomihon, kokkeibon, gōkan and hanashibon, and printed his stand-alone full color prints of "kabuki" actors and warriors.
Despite his promising debut, the young Kuniyoshi failed to produce many works between 1818 and 1827, probably due to a lack of commissions from publishers, and the competition of other artists within the Utagawa school (Utagawa-ryū). However, during this time he did produce pictures of beautiful women ('bijin-ga') and experimented with large textile patterns and light-and-shadow effects found in Western art, although his attempts showed more imitation than real understanding of these principles.
His economic situation turned desperate at one point when he was forced to sell used tatami mats. A chance encounter with his prosperous fellow pupil Kunisada, to whom he felt (with some justice) that he was superior in artistic talent, led him to redouble his efforts (but did not create any lingering ill-feeling between the two, who later collaborated on a number of series).
During the 1820s, Kuniyoshi produced a number of heroic triptychs that show the first signs of an individual style. In 1827 he received his first major commission for the series, One hundred and eight heroes of the popular Suikoden all told (Tūszoku Suikoden gōketsu hyakuhachinin no hitori), based on the incredibly popular Chinese tale, the Shuihu Zhuan. In this series Kuniyoshi illustrated individual heroes on single-sheets, drawing tattoos on his heroes, a novelty which soon influenced Edo fashion. The Suikoden series became extremely popular in Edo, and the demand for Kuniyoshi’s warrior prints increased, gaining him entrance into the major ukiyo-e and literary circles.
He continued to produce warrior prints, drawing much of his subjects from war tales such as Tale of the Heike (Heike monogatari) and The rise and fall of the Minamoto and the Taira (Genpei Seisuiki). His warrior prints were unique in that they depicted legendary popular figures with an added stress on dreams, ghostly apparitions, omens, and superhuman feats. This subject matter is instilled in his works The ghost of Taira no Tomomori at Daimotsu bay (Taira Tomomori borei no zu) and the 1839 triptych The Gōjō bridge (Gōjō no bashi no zu), where he manages to invoke an effective sense of action intensity in his depiction of the combat between Yoshitsune and Benkei. These new thematic styles satisfied the public’s interest in the ghastly, exciting, and bizarre that was growing during the time.
The Tenpō Reforms of 1841–1843 aimed to alleviate economic crisis by controlling public displays of luxury and wealth, and the illustration of courtesans and actors in ukiyō-e was officially banned at that time. This may have had some influence on Kuniyoshi's production of caricature prints or comic pictures (giga), which were used to disguise actual actors and courtesans. Many of these symbolically and humorously criticized the shogunate (such as the 1843 design showing Minamoto no Yorimitsu asleep, haunted by the Earth Spider and his demons) and became popular among the politically dissatisfied public. Timothy Clark, curator of Japanese art at the British Museum, asserts that the repressive conventions of the day produced unintended consequences. The government-created limitations became a kind of artistic challenge which actually encouraged Kuniyoshi’s creative resourcefulness by forcing him to find ways to veil criticism of the shogunate allegorically.
During the decade leading up to the reforms, Kuniyoshi also produced landscape prints (fūkeiga), which were outside the bounds of censorship and catered to the rising popularity of personal travel in late Edo Japan. Notable among these were Famous products of the provinces (Sankai meisan zukushi, c. 1828–30)—where he incorporated Western shading and perspective and pigments—and Famous views of the Eastern capital in the early 1830s, which was certainly influenced by Hokusai's early-1830s Thirty-six Views of Mount Fuji (Fugaku sanjūrokkei). Kuniyoshi also produced during this time works of purely natural subject matter, notably of animals, birds and fish that mimicked traditional Japanese and Chinese painting.
In the late 1840s, Kuniyoshi began again to illustrate actor prints, this time evading censorship (or simply evoking creativity) through childish, cartoon-like portraits of famous kabuki actors, the most notable being "Scribbling on the storehouse wall" (Nitakaragurakabe no mudagaki). Here he creatively used elementary, childlike script sloppily written in kana under the actor faces. Reflecting his love for felines, Kuniyoshi also began to use cats in the place of humans in kabuki and satirical prints. He is also known during this time to have experimented with wide composition, magnifying visual elements in the image for a dramatic, exaggerated effect (ex. Masakado's daughter the princess Takiyasha, at the old Soma palace).
In 1856 Kuniyoshi suffered from palsy, which caused him much difficulty in moving his limbs. It is said that his works from this point onward were noticeably weaker in the use of line and overall vitality. Before his death in 1861, Kuniyoshi was able to witness the opening of the port city of Yokohama to foreigners, and in 1860 produced two works depicting Westerners in the city (Yokohama-e, ex. View of Honchō and The pleasure quarters, Yokohama). He died at the age of 63 in April 1861 in his home in Genyadana.