The Six Million Dollar Man star will play a detective called Burton in the CBS drama, TV Guide reports.
Burton worked on a case in 1957 that went cold and agrees to help Mac (Gary Sinise) when a very similar investigation opens up in the present day.
The episode is also expected to feature Greek stars Spencer Grammer and Aaron Hill.
Majors has recently guest starred in shows such as Grey's Anatomy, $#*! My Dad Says, Raising Hope and Community.
CSI: NY returns on Friday on CBS, while Majors' episode is due to air in the spring.