The tie-up is Npower's first association with the charity's flagship fundraiser. It is the first time the event has been sponsored by a utilities company.
An ad campaign through Npower's agency Isobel will promote its involvement and encourage consumers to take part by giving details of how to register.
A campaign will also run through its business-to-business division.
The Macmillan event raised more than £4m last year and attracted 2m participants.
Previous sponsors include Kit Kat and Nescafe.
Npower is better known for its sports sponsorship; it is the official sponsor of England cricket and the first brand sponsor of Wembley Stadium. Kevin Peake, Npower's head of brand, said the tie-up marked a wider increase in CSR activity.