O'Donohue is a surname, and may refer to:
- Becky O'Donohue (born 1980), reality television participant
- Daniel Anthony O'Donohue (20th century), United States Ambassador to Burma
- Edward O'Donohue (born 1974), Australian politician
- Jessie O'Donohue (born 1980), reality television participant
- John O'Donohue (1956–2008), poet and philosopher
- John F. O'Donohue (21st century), American actor
- Michael O'Donohue (1835–1912), Irish-American builder and architect
- Peter O'Donohue (born 1923), former Australian rules footballer
- Ryan O'Donohue (born 1984), American voice actor
- Tony O'Donohue (born 1933), Canadian politician
- William O'Donohue (born 1957), American psychologist