Papworth Trust, the larger of the two organisations, has a workforce of 650 and had an income of nearly £21m in 2011/12.
It provides care support services, leisure activities and practical help to people with disabilities in the east of England and the East Midlands.
Workwise, which provides work-based training to adults with mental ill health, employs 15 people and had a turnover of £529,000 in 2011/12.
The trust said Workwise would be absorbed in about six weeks and that the new organisation would be called the Papworth Trust Charity. But Workwise will continue to use its name and identity where it currently operates in Suffolk.
Adrian Bagg, chief executive of the Papworth Trust, will head the new organisation. Valerie Beresford, chief executive of Workwise, will continue to lead it under a new job title, which has yet to be announced.
The board for the new organisation had yet to be finalised, the trust said.
"By working together Workwise and the Papworth Trust will be able to offer more brilliant services to more people in the future," said Bagg. "In the meantime, I want to reassure people that it will be business as usual."
A spokesman for the trust said the new organisation would employ "more than 500 staff" but would not rule out potential redundancies, saying only that "no significant changes are planned".
Workwise said that all 15 of its staff had been invited to join the new charity
"We make a huge difference to the lives of the people we help," said Beresford. "This is a great opportunity for us to extend and offer our unique services to even more people."