Army spokesman Ronald Rvivanga told local media that two long-serving generals, Major General Aloys Muganga and Brigadier General Francis Mutiganda, had been sacked for "indiscipline".
"According to the law, this means that they have to hand over military equipment and leave the army without any benefits, because of what they did," he said, without elaborating.
Another 14 officers were also dismissed along with more than 200 other members of the military, the Rwanda Defence Force said in a statement.
On Tuesday, Kagame had announced a reshuffle in several top security posts, without giving any reasons for the move.
The changes come amid tensions with the Democratic Republic of Congo which accuses its smaller neighbour Rwanda of backing rebels sowing chaos in the east of the mineral-rich country.
Kagame said Juvenal Marizamunda had been appointed defence minister, replacing Albert Murasira who had served in the post since 2018.
The 58-year-old Marizamunda was previously the head of Rwanda's correctional services, and also a former deputy inspector general of police.
Kagame appointed Mubarak Muganga as the new chief of defence staff, and Vincent Nyakarundi as army chief of staff, a statement from his office said.
Jean Bosco Ntibitura was named director general in charge of internal security in the National Intelligence and Security Services (NISS).
Other changes were also made to command roles in the Rwandan force which has been deployed in Mozambique since 2021 to counter a jihadist insurgency.
- 'Normal thing ' -
Kagame presided over the swearing-in of Marizamunda and other officials on Wednesday, describing the changes as "a normal thing" without making direct reference to the mass sackings.
"The goal remains the same... the only new thing is that a person is moved from one position to another," he said in a brief speech in the local Kinyarwanda language.
"The work has to be done in a capable manner... to be done with an understanding of the seriousness of these responsibilities."
Of the sacked generals, Muganga had been appointed commander of mechanised forces in 2019, while Mutiganda had been in charge of external security at the NISS until October 2018 when he was called back to RDF headquarters in an unspecified role, local media reports said.
"He (Kagame) has also authorised the dismissal of 116 other ranks and approved the rescission 1of 12 other ranks," the RDF statement said, adding that the moves were effective immediately.
Kagame is no stranger to sacking the top military brass, some of whom have previously been sentenced to lengthy jail terms for insurrection or fled to exile.
In 2016, retired Brigadier General Frank Rusagara was jailed for 20 years for inciting insurrection before his sentence was reduced to 15 years.
Rusagara was charged alongside Colonel Tom Byabagamba who previously served as Kagame's head of the presidential guard unit.
Last week, the Democratic Republic of Congo's army accused the Rwandan military and the M23 rebel group of planning to attack the eastern Congolese city of Goma.
The Tutsi-led M23 has captured swathes of territory in North Kivu province since taking up arms in late 2021 after years of dormancy, with over one million people displaced by the fighting.
The DRC has repeatedly accused neighbouring Rwanda and its Tutsi-led government of backing the M23, a charge backed by several Western countries and independent UN experts, but one that Kigali denies.
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