Creations from more than 245 artists, scientists and curators from 55 different countries will be on display along a route through the city, winding through art galleries and churches to more unusual locations such as a cinema, and outdoors.
Work from anthropologists, biologists, theorists, engineers, political activists, a hypnotherapist, a psychoanalyst and a zoologist will be included in the show which deliberately plays with the question of what is art.
Visitors expecting a fun, cultured day out could find themselves instead challenged though, as the event's artistic director Carolyn Christov-Bakargiev explained that "documenta in Kassel is intentionally uncomfortable, incomplete, nervously lacking.”
"I think confusion is really wonderful," she added.
"What these participants do and what they exhibit at documenta may or not be art," said the US-born Christov-Bakargiev. "The boundary between what is art and what is not has become less important."
Participants include Germany's Rosemarie Trockel, who erected a "House for Pigs and People" at the 1997 edition, and South African painter and film-maker William Kentridge.
China's Song Dong will unveil a garbage heap that has already been completely colonised by freshly grown grass while Frenchman Pierre Huyghe will be showing off a compost heap.
An ambitious plan to display El Chaco, the world's second heaviest meteorite weighing 37 tonnes, was eventually abandoned. Instead, the attempt will be documented.
Kassel, in the central state of Hesse, hosts the world-famous documenta art fair every five years.
German President Joachim Gauck was there to mark the occasion, arriving early on Saturday. He was greeted by crowds of excited art-fans waiting in one of the city's main squares before taking a tour of the Fridericianum museum which is hosting part of the documenta.
And for the first time, parallel events will take place in Kabul, Cairo and Canada's Banff National Park. The Afghan capital will host an exhibition, film series and part of a photo collage whose second half can be seen in Kassel. The show runs until September 16.