Foreign Minister Salahuddin Rabbani, Public Works Minister Mahmood Baligh and Social Services Minister Nasreen Oryakhel all failed to win confidence votes in parliament and were declared to have been dismissed by the speaker.
All three were dismissed for their performance and failure to spend all allocated budgetary funds on time, in accordance with provisions in the Afghan constitution which gives parliament the power to sack ministers. Fourteen other ministers are due to face similar confidence votes, according to Reuters.
At a time when the Taliban insurgency is threatening security across Afghanistan, the move creates further confusion for the national unity government which has been mired in infighting ever since it was set up following the disputed election of 2014.
A suicide attack by Taliban militants on the German consulate in the northern city of Mazar-i-Sharif this week killed four people and wounded more than 100 others.
Former rivals Ghani and Chief Executive Abdullah Abdullah have presided over an uneasy alliance that also includes the volatile vice president General Rashid Dostum and has featured regular rows between the main leaders.
Patched together with US backing after accusations of electoral fraud on both sides, the government was supposed to have overseen fresh parliamentary elections and a constitutional grand council to re-establish political legitimacy.
However, a two-year deadline has passed with none of the promised steps taken, leaving question marks over the future of the government at a time when political uncertainty is already being stoked by rising ethnic tensions.