The company's Board has named co-founder and Chairman Jack Dorsey as Interim CEO as the Board conducts a search for the company next head, Twitter said in a statement.
Dorsey was the first Chief Executive of the company.
Costolo will continue to serve on Twitter's Board of Directors, it added.
"I am tremendously proud of the Twitter team and all that the team has accomplished together during my six years with the company...There is no one better than Jack Dorsey to lead Twitter during this transition," Costolo said.
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Twitter's Board has formed a search committee to lead the hunt for a permanent CEO. The committee, chaired by the Board's lead independent director Peter Currie, will include Peter Fenton and Evan Williams.
The committee will retain a leading executive search firm to assist in conducting a global search, which will consider both internal and external candidates for the position.
Even though the company has grown its monthly active users by 18 per cent over last year to 302 million, the pace of growth seems short of investor expectations.
Defending Costolo, Dorsey on a conference call said his departure had nothing to do with the recent earnings report.
"This transition is not the result of anything more than Dick deciding to move on as CEO, and there's no connection with our results," he added.
Costolo, who led Twitter for six years, said: "The scrutiny of the company would intensify if I remained CEO while the search process takes place."
On a maiden trip to India recently, Costolo had expressed confidence in the potential of the Indian market saying it is one of the fastest growing markets for the micro-blogging giant in terms of users and that the company will expand its sales team in the country.
The US-based firm also reaffirmed its outlook for the second quarter of 2015.
The company continues to expect revenue to be in the range of USD 470 million to USD 485 million.