Brook last fought in September when he took a challenging fight up at middleweight against unbeaten Gennady Golovkin but won plenty of plaudits before he was stopped in the fifth round.
Spence meanwhile remains unbeaten in his professional career and has been tipped for greatness by many in the US.
The pair got underway around 10.45pm after ring walks as scheduled at 10.30pm.
George Groves topped the support action and got his fourth shot at a world title, taking on Fedor Chudinov for the vacant WBA super-middleweight belt.
He produced a brilliant sixth round stoppage and dedicated his win to Eduard Gutknecht, who was left disabled by a bout against Groves in November.
David Allen fought for a global title but lost a split decision to Lenroy Thomas while Robbie Fowler's cousin Anthony marked his professional debut with a first-round knockout.
Two more of Eddie Hearn's Olympians were in action as Joe Cordina and Lawrence Okolie both scored similar round one stoppages.