While growing up with and being heavily influenced by many blues, jazz and R&B musicians in his father's immediate circle, Otis began to gravitate towards the popular music of his generation such as Jimi Hendrix, Arthur Lee (of the band Love), and Sly Stone.

Guest musicians on his debut included Johnny, Leon Haywood, Al McKibbon, Wilton Felder.

Some of the artists Otis performed and recorded with during that time include Frank Zappa (having played electric bass on the instrumental, "Peaches en Regalia" from the 1969 album Hot Rats),[11] Etta James, Eddie Vinson, Richard Berry, Louis Jordan, and Bobby 'Blue' Bland, among many others.

The album Otis received the most recognition for was his second Epic Records release in 1971, Freedom Flight, which featured his hit "Strawberry Letter 23".

Even though Otis played most of his own parts in the studio, the lineup on this album was quite extensive, including keyboardist George Duke and Aynsley Dunbar of Frank Zappa, Journey and Whitesnake fame.

After the album's release, Otis was approached by Billy Preston on behalf of The Rolling Stones, asking him to join the band for their upcoming world tour.

Due in part to this regained interest, the album was re-released on April 3, 2001, by David Byrne's independent label Luaka Bop Records.

Otis is featured in every one of his father Johnny's books,[citation needed] as well as Alligator Records Presents West Coast Blues, issued in August 1998.

He has also fronted a 13-piece rhythm-and-blues orchestra, The New Johnny Otis All-Stars, continuing his grandfather's Big Band legacy.

With The Johnny Otis Show With Bo Diddley With Guitar Slim Green With Etta James and Eddie "Cleanhead" Vinson With Al Kooper With Preston Love With Gerald Wilson Orchestra With Frank Zappa With Jimmy Vivino With Mark Lotito