Daniel Radcliffe and Jon Hamm will both reprise their roles when the show - based on the works of playwright Mikhail Bulgakov - returns as part of the channel's Playhouse Presents strand.
Radcliffe plays the younger self of Hamm's Russian doctor in the series, which picks up in the small village of Muryevo in 1918 with the character battling a morphine addiction.
Adam Godley will reprise his role as The Feldsher, with newcomer Margaret Clunie set to star as beautiful young aristocrat Natasha.
Hamm said of his return: "I'm thrilled to come back to our wonderful, weird, wild world of A Young Doctor's Notebook. Series one was an absolute blast to work on and I'm looking forward to continuing this bizarre adventure."
Radcliffe commented that he had "absolutely no hesitation" in signing up to appear in a second run of the drama.
He said: "I had an incredible time working with the multi-talented Jon Hamm and of course am a huge fan of Mikhail Bulgakov's work and so was thrilled when I was told a second series had been commissioned.
"I am also greatly looking forward to working with our new director Robert McKillop and cannot wait to commence filming this summer."
Director at Sky Arts James Hunt has described the show's first series as "the channel's most successful programme to date".
A Young Doctor's Notebook & Other Stories will be available on Sky Arts 1 HD and On Demand later in 2013.