According to the French news agency, the stolen books contained important ideas about Darwin's theory of evolution and sketches of his famous "Tree of Life".
The leather notebook was written by a British scientist in 1837 after returning from a voyage of the Royal Navy ship HMS Beagle.
According to the Cambridge University Library, the books were worth millions of pounds.
In one of these books, Charles Darwin drew a diagram in which he showed the various possibilities for the evolution of species.
Later, in his book On the Origin of Species, published in 1859, he gave a better picture.
The University of Cambridge's extensive library declared these notebooks lost in 2001 when they were moved out of the Special Collections Strong Rooms for photography.
It has long been thought that they were incorrectly placed inside the building, which contains about 10 million books, maps, and manuscripts, as well as the world's most important Darwin archives.
However, a massive search this year did not find the books.
"The authorities have concluded that the books may have been stolen," the library said in a statement.
The statement said local police had been notified and the books had been added to Interpol's database of stolen artworks.
University librarian Jessica Gardner released a video statement appealing for help.
"It is very unfortunate for me that these notebooks have not been found despite extensive searches over the last 20 years," he said.
The librarian added that the library has made significant improvements to its security systems since then.
He said the library's former or current staff, the book trade, or researchers may have information in this regard.
"I would ask anyone who thinks they know about notebooks, please help," said Jessica Gardner.
The appeal was made on November 24, which is considered Evolution Day due to the publication date of the book Evolution of the species.
