Spencer currently plays Dr. Robert Chase on Fox's medical drama House, opposite lead Hugh Laurie.
According to Deadline, the 33-year-old actor will be starring in an NBC pilot called Chicago Fire.
Spencer's character will be Matthew Casey, a Chicago firefighter, dealing with a separation from his wife. Also cast in the pilot is Charlie Barnett, who will be playing a rookie firefighter named Peter Mills.
This new move makes Spencer the first House cast member to book a new series regular role on another network.
Fox announced earlier this year that House will be cancelled after an eight-season run on the network.
It was recently reported that Lisa Edelstein, who played Dr. Cuddy on the show for several years, will not be returning for the finale of the show.