Whitfield plays the title character in the show, which has been renewed for a second season and was set to air next year.
The actor said he is resuming aggressive treatment for a recurrence of non-Hodgkin lymphoma.
"It's with a deep sense of disappointment that I must step aside from such an exceptional project as 'Spartacus‚' and all the wonderful people involved. It seems that it is time for myself and my family to embark on another extraordinary journey. Thank you sincerely for the support so far," Whitfield said in a statement.
"Our hearts and prayers are with Andy and his family during this difficult time," Starz President and Chief Executive Officer Chris Albrecht said. "Andy is not only an incredible actor whose portrayal of Spartacus made an indelible impression on Starz audiences, he is also an amazing human being whose courage, strength, and grace in the face of adversity have inspired all of us."
Starz said no decision has been made yet about the future of the series.