The deal reduces his holding in the company from 7.13% to 5.71%, according to a Stock Exchange announcement.
His remaining stake is likely to be worth in excess of £400m depending on the share price at the time.
Earlier this year his co-founder Peter Hargreaves sold £550m of his shares.
Mr Lansdown and Peter Hargreaves founded the firm over 30 years ago and retain significant shareholdings but are no longer active in running the business.
The two men, both accountants by training, initially set up the company in 1981 trading from a spare bedroom. They sold off the page investments in unit trusts and found a willing audience of DIY investors.
The company has now grown to become one of the largest fund supermarkets and investment providers in the UK although it has faced criticism for its role in promoting the failed Woodford funds.
Mr Lansdown, 68, who lives in Guernsey, sold the stake this week through his Guernsey company and has so far sold just under £300m of shares this year, according to a report from Bloomberg.
He told Bloomberg Wealth: “It was just an opportune time, with the market spiking up a bit on the back of the vaccine news.”
“I thought it was appropriate to take the opportunity to bank some money to reinvest elsewhere and support investments I’ve already got.”
Mr Lansdown told Bloomberg the money would be used to redevelop his hotel on the island and the area near a sport stadium he owns in Bristol.