Jonathan was born into a Jewish family in Cape Town, South Africa to Gershon and Gaby Shapiro.

He studied architecture at the University of Cape Town but found it unsatisfying and moved to the art campus, Michaelis.

In 1983 he became active in the newly formed anti-Apartheid movement, the United Democratic Front and as a result was arrested under the Illegal Gatherings Act and, subsequently, monitored by military intelligence.

After his military service he applied for and was awarded a Fulbright scholarship to study cartooning at the School of Visual Arts in New York for two years.

[1] The name Zapiro was derived from the nickname of a fellow pupil at Rondebosch Boys' High School, Martin Szapiro, whose friends called him Zap.

[4] Zapiro's caricatures also appear in the form of puppets on the satirical television and web show ZANEWS, a Spitting Image type of programme he helped launch in 2009 alongside producer Thierry Cassuto.

His exhibition "Jiving with Madiba" was held at the South African Jewish Museum in Cape Town from 14 July to 27 November 2011.

He has been an invited participant in cartoon events in Cameroon, Botswana, Australia, France, the UK, the Netherlands and Italy.

[14] In 2006, former Deputy President of South Africa Jacob Zuma furthered his claim of being "tried by the media" and threatened to bring defamation action against various elements of the press for remarks that he alleged were defamatory.

[17] On 21 May 2010 the Mail and Guardian published a strip from Zapiro depicting Muhammed, as part of Everybody Draw Mohammed Day.

In 2016 a cartoon he published depicting National Prosecuting Authority head Shaun Abrahams as a monkey was criticised for being racist.