The attack on Malian soldiers in Indelimane in the Menaka region near the Niger border is one of the deadliest in the last decade.
At least 54 people have been killed in Mali following a jihadist attack on Friday.
The Malian army were targeted on a military post in Indelimane, in the Menaka region near the border with Niger, according to the government.
At least 53 soldiers and one civilian are understood to have died.
It is the second major assault on soldiers in a month, and one of the deadliest in the last decade.
Malian communications minister Yaya Sangare confirmed the deaths in a tweet, saying that the identification of bodies is now under way.
He said “significant material damage” had also been caused.
Mr Sangare later told the Associated Press: “Reinforcements have been sent to the scene and the situation is under control with the support of the French military, which is helping to evacuate the wounded.”
Ten people are believed to have survived.
Islamic State has claimed it was behind the attacks.
The troubled West Africa border has been plagued by violence since al Qaeda-linked fighters took control of the north of the country in 2012.
They were successfully pushed back in a French-led military campaign a year later, but attacks are now on the rise.
Soldiers are struggling to contain the regrouped jihadists, who are moving from the north of the country into new areas.
Bloodshed has also spread to other countries in the region.
The worsening ethnic and jihadist violence also led to hundreds of civilian deaths last year.
The attack is expected to raise tensions in the capital of Bamako, where protests have already taken place in the streets.
Military families say soldiers are not being properly protected, and do not have adequate resources to tackle the armed groups in the vast desert landscape.