Ganwyd Margo yn [[Hamilton]], [[De Swydd LanarkshireLanark]] ac fe'i magwyd yn [[Dwyrain Kilbride|Nwyrain Kilbride]], yn un o dri phlentyn.<ref>[http://www.telegraph.co.uk/news/obituaries/10744561/Margo-MacDonald-obituary.html ''Obituary for Margo MacDonald''], telegraph.co.uk; adalwyd 5 Ebrill 2014.</ref> Nyrs meddygol oedd ei mam Jean a disgrifiodd ei thad Robert fel "dyn creulon iawn".<ref name="heraldobit">{{cite web|url=http://www.heraldscotland.com/comment/obituaries/margo-macdonald.23883336|title=''Margo MacDonald's Herald Scotland obituary''|date=5 Ebrill 2014|accessdate=5 Ebrill 2014}}</ref> Pan oedd Margo'n 12 oed, gwahanodd y fam oddi wrth y tad.<ref name="scotsman">{{cite web|url=http://www.scotsman.com/lifestyle/interview-why-margo-macdonald-is-determined-to-have-the-right-to-choose-when-she-dies-1-2564964|title=Interview: ''Why Margo MacDonald is determined to have the right to choose when she dies''|date=7 Hydref 2012|accessdate=5 Ebrill 2014}}</ref> Cafodd ei haddysg yn Academi Hamilton ac fe'i hyfforddwyd i fod yn athrawes addysg gorfforol yng Ngholeg Dunfermline wedi iddi adael yr ysgol uwchradd.<ref name="heraldint">{{cite web|url=http://www.heraldscotland.com/news/home-news/archive-interview-margo-macdonalds-crusade-to-die-with-dignity.1396623665|title=''Archive interview: Margo MacDonald's crusade to die with dignity''|date=4 Ebrill 2014|accessdate=4 Ebrill 2014|publisher=''The Herald''}}</ref>
