Upon his return in 1860, Fukuzawa became an official translator for the Tokugawa bakufu. Shortly thereafter he brought out his first publication, an English-Japanese dictionary which he called "Kaei Tsūgo" (translated from a Chinese-English dictionary) which was a beginning for his series of later books. In 1862, he visited Europe as one of the two English translators in bakufu's 40-man embassy, the First Japanese Embassy to Europe. During its year in Europe, the Embassy conducted negotiations with France, England, the Netherlands, Prussia, and finally Russia. In Russia, the embassy unsuccessfully negotiated for the southern end of Sakhalin (in Japanese Karafuto).
The information collected during these travels resulted in his famous work Seiyō Jijō (西洋事情, "Things western"), which he published in ten volumes in 1867, 1868 and 1870. The books describe western culture and institutions in simple, easy to understand terms, and they became immediate best-sellers. Fukuzawa was soon regarded as the foremost expert on all things western, leading him to conclude that his mission in life was to educate his countrymen in new ways of thinking in order to enable Japan to resist European imperialism.
In 1868 he changed the name of the school he had established to teach Dutch to Keio Gijuku, and from then on devoted all his time to education. While Keiō's initial identity was that of a private school of Western studies (Keio-gijuku), it expanded and established its first university faculty in 1890. Under the name Keio-Gijuku University, it became a leader in Japanese higher education.
In 1901, Fukuzawa Yukichi was buried at Zenpuku-ji, in the Azabu area of Tokyo. Alumni of Keio-Gijuku University hold a ceremony there every year on February 3.