"I have informed the president of the government's resignation," Straujuma told reporters.
"I see that new ideas are needed, new contributions and energy that can continue to build further on these foundations," she said, listing among her government's achievements a successful EU presidency in the first half of 2015 and strong economic growth.
The 64-year-old has been prime minister since January 2014, when she took over from Valdis Dombrovskis who resigned after the deadly collapse of a supermarket roof for which he said he felt "political responsibility".
She has notably come under fire, including from within her own Unity party, over the tax hikes included in the 2016 budget.
Teachers had also recently gone on strike over pay and the Baltic state is also divided on taking in refugees and on a deal to finance the airBaltic national airline that forced Transport Minister Anrijs Matiss from office.
President Raimonds Vejonis told reporters he would talk to all political parties before choosing a candidate to form a new government.