The agency won the business after a final head-to-head pitch against Creature London that took place last week.
M&C Saatchi was also involved in the process, which was run through the intermediary Oystercatchers.
VCCP will seek to develop the brand and raise awareness of Macmillan, which works to provide practical and emotional support to those with cancer. Its services include Macmillan nurses, a support line and grants.
In recent years, Arthur, the agency launched by the former Joshua managing director Nick Spindler, has handled much of the charity's advertising activity, which spans TV, press and direct response work.
Carly Wilson, the brand manager at Macmillan, said: "We have recently reviewed our corporate strategy and have an enormous ambition to achieve. Having gone through a tough pitch process, we're really pleased to have appointed VCCP, which saw off some strong competition, and we are looking forward to working together."
Oliver Lewis-Barclay, the business director at VCCP, said: "Macmillan already has a very strong reputation, built around its incredible work. We will be helping it raise the brand's profile so that it can support even more people living with cancer."