Wood, who is also chairman of the Rugby League International Federation, has served on the RFL board since 2001.
"I am extremely honoured and privileged to have served as chief executive of the Rugby Football League," said Wood.
"I am an unashamed rugby league fan and can think of no greater honour than to be asked to fulfil the role of CEO for the Rugby Football League.
"However, leadership presents many tests, and the greatest of these is to recognise when it is time to step out and this is the right moment to do so.
"I would like to place on record my unreserved thanks to the many excellent colleagues, the clubs and all those that I have worked with throughout the last 16 years and wish them the best of luck for the future."
Chief operating officer Ralph Rimmer will act as interim chief executive while the RFL searches for Wood's successor.
RFL chairman Brian Barwick said: "Nigel has been a superb administrator, innovator and advocate for the sport of rugby league in this country.
"His range of achievements in the sport speak for themselves and he has brought a genuine love of the game to his work over many years.
"His time at the helm of the Rugby Football League will always be looked upon warmly and with great respect."