UBarbara Mosima Joyce Masekela wazalwa ngomhlaka 18 kuJulayi 1941 eGoli. Wayengowesibili ezinganeni ezine azalelwa uPauline noThomas Selema Masekela. Umama wakhe wayengusonhlalonhle esikhungweni somndeni e-Alexander kanti ubaba wakhe wayengumhloli wezempilo futhi engumbazi wengqephu wesikhashana. UBarbara wakhulela eWitbank ngaphansi kokubuka ugogo wakhe, waze wabuyela e-Alexander Township ngo-1952. Wakhulela emndenini ohlonipha ezombusazwe. Waya e-Anglican Primary School eWitbank naseSt Michaels Anglican School e-Alexander. Ngo-1956 wabhalisa eNanda Girls Seminary Boarding School eThekwini lapho aphothula khona umatikuletsheni wakhe ngo-1960. Esikoleni samabanga aphansi baba nethuba lokuhlangana nabaholi bezenhlalo nezepolitiki abanjengoMongameli we-African National Congress (ANC) u-Chief Albert Luthuli. Ukuxhumana kukaBarbara nezibalo zezepolitiki kwenzeka esemncane kakhulu. Abantu bokuqala abahlangana nabo kwakunguHelen Navid owayenguthishanhloko esikhungweni sezempilo kanye noTata Trevor Huddleston owayefundisa esikoleni somfowabo, iSt. Ufunde ngokufika kobandlululo ngokufunda izincwadi kanye namaphephandaba kanye nokulalela izingxoxo zabazali bakhe.Ukuphothula u-matric uMasekela wenza umsebenzi wakhe ephephandabeni iNew Age. Ngemuva kwezinyanga eziyisithupha, wabhalisa ekolishi laseLesotho University of Botswana naseSwaziland. UMasekela ekuqaleni waqala ngokufundela iziqu ze-BA. NgoFebhuwari 1963 wathuthela eGhana ngemuva kwekota eyodwa kuphela eNyuvesi.