The "extended edition" of Once Upon A Time In America (249m), which was released in Italy, is/was one disc. To the best of my knowledge, nothing else anywhere near that length has been released on less than two discs.
EDIT: I done goofed--Kenneth Branagh's 1996 adaptation of Hamlet (242m) is also on only one disc. (And to answer the other previous question: AFAIK, the existing Cleopatra BD is two discs. It looks like the upcoming Region A release is two discs as well.)
Edited by Bill C. - 3/21/13 at 3:52pm