Among Obvious Corporation's projects was Twitter, a popular, free social networking and micro-blogging service. Twitter was spun out as a new company in April 2007, with Williams as co-founder, board member, and investor. In October 2008, Williams became CEO of Twitter, succeeding Jack Dorsey, who became chairman of the board.
By February 2009, Compete.com ranked Twitter the third most-used social network, based on their count of 6 million unique monthly visitors and 55 million monthly visits.
In October 2010, Williams stepped down from the CEO position, explaining that he would be "completely focused on product strategy," and appointed Dick Costolo as his replacement.
Following the announcement of Twitter's initial public offering (IPO) in 2013, the company was valued at between US$14 billion and US$20 billion.
On April 6, 2017, an article announced Williams would sell 30 percent of his stock in Twitter, for "personal reasons."
In February 2019, Williams stepped down from his role as a board member of Twitter.