One of his close friends, Chōjun Miyagi (宮城 長順 Miyagi Chōjun?) (co-founder of Gojū-ryū Karate) introduced Mabuni to another great of that period, Kanryō Higaonna (東恩納 寛量 Higaonna Kanryō?). Mabuni began to learn Naha-te (那覇手?) under him. While both Itosu and Higaonna taught a "hard-soft" style of Okinawan "Te", their methods and emphases were quite distinct: the Itosu syllabus included straight and powerful techniques as exemplified in the Naihanchi and Bassai kata; the Higaonna syllabus stressed circular motion and shorter fighting methods as seen in the kata Seipai and Kururunfa. Shitō-ryū focuses on both hard and soft techniques to this day.

Although he remained true to the teachings of these two great masters, Mabuni sought instruction from a number of other teachers, including Seishō Arakaki, Tawada Shimboku, Sueyoshi Jino and Wu Xianhui (a Chinese master known as Go-Kenki). In fact, Mabuni was legendary for his encyclopaedic knowledge of kata and their bunkai applications. By the 1920s, he was regarded as the foremost authority on Okinawan kata and their history and was much sought after as a teacher by his contemporaries. There is even some evidence that his expertise was sought out in China, as well as Okinawa and mainland Japan. As a police officer, he taught local law enforcement officers and at the behest of his teacher Itosu, began instruction in the various grammar schools in Shuri and Naha.

In an effort to popularize karate in mainland Japan, Mabuni made several trips to Tokyo in 1917 and 1928. Although much that was known as "Te" (Chinese Fist; lit. simply "hand") or karate had been passed down through many generations with jealous secrecy, it was his view that it should be taught to anyone who sought knowledge with honesty and integrity. In fact, many masters of his generation held similar views on the future of Karate: Gichin Funakoshi (founder of Shotokan), another contemporary, had moved to Tokyo in the 1920s to promote his art on the mainland as well.

By 1929, Mabuni had moved to Osaka on the mainland, to become a full-time karate instructor of a style he originally called Hanko-ryū, or "half-hard style". The name of the style changed to Shitō-ryū, in honor of its main influences. Mabuni derived the name for his new style from the first kanji character from the names of his two primary teachers, Higa(shi)onna and I(to)su. With the support of Ryusho Sakagami (1915–1993), he opened a number of Shitō-ryū dojo in the Osaka area, including one at Kansai University and the Japan Karatedō-kai dojo. To this day, the largest contingent of Shitō-ryū practitioners in Japan is centered in the Osaka area.

Mabuni published a number of books on the subject and continued to systematize the instruction method. In his latter years, he developed a number of formal kata, such as Aoyagi, for example, which was designed specifically for women's self-defense. Perhaps more than any other master in the last century, Mabuni was steeped in the traditions and history of Karate-dō, yet forward thinking enough to realize that it could spread throughout the world. To this day, Shitō-ryū recognizes the influences of Itosu and Higaonna: the kata syllabus of Shitō-ryū is still often listed in such a way as to show the two lineages.

Kenwa Mabuni died on May 23, 1952, and the lineage of the style was disputed between his two sons, Kenzō and Kenei. Currently, the Shitō-ryū International Karate-dō Kai (also known as Seito Shitō-ryū) lists Kenzō Mabuni as the second Sōke of Shitō-ryū, while the World Shitō-ryū Karate-dō Federation (also known as Shitō-kai Shitō-ryū) lists Kenei Mabuni.