He began his career under the name Guy Warren as a disc-jockey in 1944 with several jazz programmes on the Gold Coast Broadcasting Service (later Ghana Broadcasting Corporation) and Z.O.Y. Accra. He described his performance on the drums as love-making, seeing the African drums as a woman who could not be satisfied. "Is that all?" is what the drums seemed to ask after a hefty performance, to which he would respond: "I will be back for another session." While the punch and power of his playing easily tore the vinyl covering on Western-made drums, the animal skin covering the African drums remained intact. Nii Anum Telfer describes climbing on stage with Ghanaba as "a feeling I will never forget!” A firecracker would announce their entrance, “…then we were transported into another realm, a new world, a world we’ve never been in before."
Once before a US show Guy Warren appeared backstage in authentic African wear. However, the owner of the club (African Room) was trying to force him to wear what he considered an "Uncle Tom" outfit, complete with tattered straw hat, which was the norm for all Calypso and African musicians at the time. Ghanaba adamantly refused to change, thereby beginning a trend that was widely copied both on and off stage.
In 1956 his first album Africa Speaks, America Answers was recorded on the Decca Records label. It was not initially a success but quickly became an underground collector’s item, a reference point for African-inspired music. It confirmed Ghanaba’s reputation as a credible musician at the forefront of the African presence in jazz. This debut album cross-fertilized African and Western rhythms and introduced authentic instrumentation into the music. In 1964, Decca Records in collaboration with the German musician Bert Kaempfert released an orchestral version of "That Happy Feeling", the most popular song on Africa Speaks, America Answers under its original title "Eyi Wala Dong (An African's Prayer)", on Kaempfert's 1962 album A Swingin' Safari album. It became a hit, took the world by storm and went platinum.
A year later, Ghanaba worked on the release of Themes for African Drums (RCA Victor, 1958), for which he wanted to use voices, drums and a trombone, with an overall African influence. He collaborated on this album with the trombone player Lawrence Brown, who acknowledged that what Ghanaba was doing was not common in jazz and put him one step ahead of others. "My Story" saw him give the recording of his lifetime on a song he described as the story of a "man who had at long last won the battle of the spirits". Cover versions of Ghanaba's composition "Love, the Mystery Of..." were recorded by Art Blakey and by Randy Weston, who has used it as his theme song for almost 40 years.
In December 1959 readers of Drum Magazine voted Ghanaba the number one drummer in a poll conducted by the magazine.
His third recorded album, African Rhythms (Decca, 1962), was supposed to be released a year earlier with Columbia Records but the deal fell through. He then teamed up Martin Salkin and Milt Gabler of Decca Records. This album was important to him because he felt it was unadulterated and came direct from his soul.
Ghanaba is listed in the Encyclopaedia of Jazz and other reference books as a trailblazer who first injected African rhythms and instrumentation into mainstream jazz music. On one occasion in the early 1970s when he performed a concert at the Ohene Djan stadium in Accra the crowd walked out on him. It was a time when he had given up on live performances and literally hung up his drumsticks because of the uninspiring cultural atmosphere and lack of respect shown to his art by the political structures and society. He only released two albums in the 1970s: The African Soundz (RCA Victor, 1972) and The Divine Drummer (1978).
He asked Nii Anum Telfer who worked with him to trace a letter from Africa Obonu, later to be known as Ghanababii, a drums and percussion ensemble based at La in Accra that had written to Ghanaba. It was after Ghanababii were contacted that he began to perform again. He played many gigs, including the monthly Free South Africa shows that he and Nii Anum Telfer organized at the Accra Community Centre in solidarity with Nelson Mandela, who was at the time in prison, and the people of South Africa who were fighting against apartheid. By March 1979 he had brought together Zagba Oyortey, Ofei Nkansah, Wendy Addae, Dorothy Gordon (aiti-KACE), Akuoko, Akwasi Adu Amankwa, Anthony Akoto Ampaw (Che-Che), Tsatsu Tsikata, Fui Tsikata, Prof. Akilagpa Swayer, Nii Kwate Owoo, George Quaynor-Mettle, Takyiwa Manu, Kwaku Opoku, F. Ato Austin and James Quarshie. Their aims and objectives were to collect, preserve, document and promote African arts and culture. During the Soul to Soul concert held in Accra on 8 March 1971 Ghanaba gave a thunderous performance with an ensemble of gourd players from Benin.
By the early 1980s Ghanaba had moved to Achimota and had his second daughter Gye Nyame Hosanna Ghanaba. In 1983, in search of more peace and quiet, he moved to Korleman village. Although he released no major albums during this period, he remained active in the music industry in Ghana. He was instrumental in setting up the Musicians Union of Ghana and led the union as its National President from 1989 to 1992, advocating the need for Ghanaian musicians to use indigenous musical instruments; these were not empty words since he lived what he preached. Ghanaba considered his greatest work to be the African talking drums interpretation of the "Hallelujah Chorus" by Handel. In 1981, in recognition of his versatility and the mystical powers he had over the African drums, he was enstooled as Odomankoma Kyrema (The Divine Drummer) by Aklowa, the African Heritage Village, based at Takley, near London, England. Three historical concerts in dedication of Africa’s Contribution to the World took place at London's Royal Albert Hall in March 1986. From this period he performed his music at various shows at the National Theatre, the Goethe-Institut, the Dubois Centre and other venues in Ghana. In 2001, he participated centrally as The Divine Drummer in the stage show written by Margaret Busby, Yaa Asantewaa: Warrior Queen, a co-production between Adzido Pan-African Dance Ensemble, the African and Caribbean Music Circuit, Black Voices, the Pan-African Orchestra and West Yorkshire Playhouse, which toured the UK and subsequently had performances in Accra and Kumasi.
In addition to learning from books Ghanaba liked to share ideas with other worthy musicians. Introduced to Robyn Schulkowsky, a leading female drummer from the USA living in Germany, by Sabine Hentzch of the Goethe-Institut in Accra, he said: "My whole life I thought I was the only one on earth who is crazy enough to deal with music the way I do. And now I have to recognize that there is another one; a woman, a white one." In 1992 he also set up and edited Hwe (Observe), a weekly newspaper.
In February 2005 during the Black History Month celebrations, Ghanaba was awarded a "Life Time Achievement Award" at the W. E. B. Dubois Centre in Accra. On 18 January 2008, after a lifetime of producing extraordinary music, Ghanaba handed over his drumsticks to his son Glenn "Ghanababa" Warren at a ceremony organised at the National Theatre in Accra.
Ghanaba died on 22 December 2008. On 21 June 2009, a tribute was held at the Jazz Gallery in New York, featuring Randy Weston, with guests including Obo Addy and Kwaku Martin Obeng.