In the late 1960s he became interested in mysticism and psychedelia, deepened by travels in India. Because his work was so attuned to 1960s pop culture, he has often been (unfairly) described as the "Japanese Andy Warhol" or likened to psychedelic poster artist Peter Max, but Yokoo's complex and multi-layered imagery is intensely autobiographical and entirely original. By the late 60s he had already achieved international recognition for his work and was included in the 1968 "Word & Image" exhibition at the Museum of Modern Art in New York. Four years later MoMA mounted a solo exhibition of his graphic work organized by Mildred Constantine. Yokoo collaborated extensively with Shūji Terayama and his theater Tenjō Sajiki. He has also starred as a protagonist in Nagisa Oshima's film Diary of a Shinjuku Thief.
In 1968 Yukio Mishima claimed, "Tadanori Yokoo's works reveal all of the unbearable things which we Japanese have inside ourselves and they make people angry and frightened. He makes explosions with the frightening resemblance which lies between the vulgarity of billboards advertising variety shows during festivals at the shrine devoted to the war dead and the red containers of Coca Cola in American Pop Art, things which are in us but which we do not want to see." 
In 1981 he unexpectedly "retired" from commercial work and took up painting after seeing a Picasso retrospective at the Museum of Modern Art (New York). His career as a fine artist continues to this day with numerous exhibitions of his paintings every year, but alongside this he remains fully engaged and prolific as a graphic designer.