Mukherjee was received at the VVIP Lounge at Tribhuvan International Airport by his Nepalese counterpart Bidya Devi Bhandari. He arrived at the head of a 36-member delegation.
Authorities shut down the Airport ahead of Mukherjee's arrival.
The airport administration issued a public notice on Wednesday morning stating that all international flights will be stopped 25 minutes ahead of his arrival and another 25 minutes after he lands.
Over 5,000 security personnel have been deployed in the capital city for the visit.
All major roads inside Kathmandu that President Mukherjee will be travelling on have been shut for public use.
The government has announced a public holiday in honour of the visiting Indian President.
The last Indian President to visit Nepal was K.R. Narayanan on May 28, 1998.
Mukherjee is slated to hold a meeting with Bhandari later in the day at the Sheetal Niwas, the official residence of the President.
On Thursday, Mukherjee will offer prayers at the Pashupatinath temple and will visit the Kathmandu University, where he will be honoured with an honorary degree. He will participate in a seminar hosted by India Foundation.
He will also attend a dinner hosted by Prime Minister Pushpa Kamal Dahal 'Prachanda'.
On Friday, he will visit Pokhara and Janakpur. He is to perform a puja at the Janakpur-based Janaki Temple.
Mukherjee will return to Kathmandu on the same day and head back to India.