Debuting as a professional boxer on March 26, 1992 Yosuke Nishijima compiled a 24–2–1 record, and over the course of his career, won the WBO NABO Cruiserweight title, the OPBF Cruiserweight title and the World Boxing Federation Cruiserweight title. His last boxing bout, a two-round TKO loss to Cecil McKenzie in a California State Cruiserweight title fight, took place on July 10, 2003.

On February 26, 2006 Nishijima debuted in mixed martial arts, at PRIDE 31, taking on Mark Hunt and losing by KO.

Currently Nishijima's record in mixed martial arts is 0–5 with most recent loss to Melvin Manhoef by TKO, took place on December 31, 2007 at K-1 PREMIUM 2007 Dynamite!!.

In 2009 Nishijima competed in two K-1 style kickboxing bouts. He lost to Peter Aerts by KO due to a right leg kick on August 11, 2009 at the K-1 World Grand Prix 2009 in Tokyo Final 16 Qualifying GP. On New Year's Eve 2009 he fought another K-1 style kickboxing bout when he took on Ray Sefo at Dynamite!! 2009 and lost by unanimous decision. He was not allowed to kick during this match, as he was wearing boxing shoes, which ended up giving him a large disadvantage against the Samoan. His kickboxing record is currently 0–2.

In his retirement match, Nishijima defeated Bob Sapp under kickboxing rules at Legend 4 in Kumamoto, Japan on November 17, 2013, although he was not allowed to kick as he chose to wear boxing shoes. He dropped Sapp with a body shot. Sapp stood back up but he finished the business with body shots followed by couple of right hooks.