Author Miguel de Cervantes, whose man of La Mancha first appeared in 1605, will be saluted with exhibitions, public readings, films and debates, The Telegraph reported Friday.
The novel is widely considered among the greatest works of literature, and ministers plan to use the anniversary to promote Spanish culture abroad and literacy at home.
"This celebration will reach every public library in every corner of Spain," said Carmen Calvo, the culture minister. "The most important tribute you can pay the book is to read it."
"Don Quixote" has been variously described as the first great European novel, the first work of modern literature and the foundation of Latin American fiction.
In 2002, the novel was voted the best book of all time by a group of 100 writers.