Last July, Channel 4 chief executive David Abraham introduced a new organisational structure, meaning digital channels such as More4 and E4 would no longer have dedicated controllers.
At the time, Abraham said that Jain - the then controller of E4 and Big Brother - would be handed a new role within Channel 4. However, it has now been announced that she will not return to the broadcaster after her maternity leave expires.
Discussing her time in charge of E4, Jain said: "It has been an enormous privilege and great fun to work with some of the most highly respected and dynamic people in television. I am very sad to leave but grateful to have had the opportunity to make a difference and leave my imprint on E4."
Abraham added: "Angela is leaving E4 in great shape and I would like to thank her for leading the channel for the past two years. Her legacy is a string of critically-acclaimed, top-performing shows, from Misfits and Glee to Inbetweeners and Skins."
Oldroyd is also stepping down from her post as Channel 4's channel manager, in which she was responsible for T4 and 4Music.
Paul Mortimer, the acting head of E4 during Jain's maternity leave, will return to the role of channel manager upon the arrival of new Channel 4 chief creative officer Jay Hunt.