The Weir Charitable Trust supports Scottish groups, individuals or charities providing services in the country.
The Weirs won £161m in the EuroMillions lottery in July 2011, the largest jackpot won in Europe.
They said: "We are delighted that the Weir Charitable Trust is now open for business.
"Since we won the EuroMillions lottery, it has been a privilege to be in a position to provide support where we could.
"But we have been looking at finding a more structured way to share our good fortune on an ongoing basis across Scotland.
"It has taken some time to set up, but we are pleased that the trust will now allow us to do that at a time when good causes in Scotland are struggling."