Marc Lore and Vinit Bharara, founders of the Amazon owned Quidsi group, have left the company to work on other projects.
The company was bought by Amazon in 2011 for around $545 million (£365.8 million) but remained operationally independent and ran out of its headquarters in New Jersey.
The purchase was Amazon's third largest acquisition to date, with $1.2 billion (£810 million) for online clothing and shoes store Zappos.com in 2009 being the biggest. Last year the company bought warehouse robotics firm Kiva Systems for $775 million (£520 million).
Lore was Quidsi's chief executive officer and Bharara its chief operating officer. Employees were notified of their approaching departure in April. Maria Renz, the former vice president of media at Amazon, took over as Quidsi's CEO on 1 July.
Tim Volkema, a spokesman for Quidsi told Bloomberg: "Lore and Bharara announced their decisions to employees in April and have been working with Renz since then to ensure a seamless transition."
A number of Executives and founders who have joined Amazon through acquisitions have remained with the company including Mick Mountz, founder and CEO of Kiva Systems, Tony Hsieh, who was CEO of Zappos when Amazon bought it, and Otis Chandler, founder and CEO of Goodreads.