He will go up against former Strikeforce heavyweight champion Alistair Overeem in one of the year's most anticipated bouts Friday night.
It was recently determined that the winner of the bout will face current UFC heavyweight champion Junior dos Santos, who defeated Cain Velasquez on the first UFC on FOX show.
After a second fight with diverticulitis, Lesnar will return to the cage for the first time in over a year to face Overeem. He was last seen getting pummeled by Velasquez in Oct. 2010.
Overeem will enter the bout with an extensive 35-11 record, including a current 10-fight win streak with victories over Brett Rogers, Fabricio Werdum and Kazuyuki Fujita.
In the co-main event, lightweight standouts Nate Diaz and Donald Cerrone will fight to determine the next top contender in the division.
Brock Lesnar (266) vs. Alistair Overeem (263)
Donald Cerrone (156) vs. Nate Diaz (156)
Jon Fitch (171) vs. Johny Hendricks (170)
Alexander Gustafsson (203) vs. Vladimir Matyushenko (205)
Jim Hettes (145) vs. Nam Phan (146)
Junior Assuncao (145) vs. Ross Pearson (145)
Danny Castillo (156) vs. Anthony Njokuani (154)
Dong Hyun Kim (171) vs. Sean Pierson (171)
Efrain Escudero (155) vs. Jacob Volkmann (155)
Luis Ramos (171) vs. Matt Riddle (170)
Manny Gamburyan (146) vs. Diego Nunes (145)