The circumstances of Tuesday's raid in a region hit by local militias often organised along community lines, as well as criminal networks, have not been released.
The park's HQ at Lusinga in Katanga province was "the target of an armed raid carried out by a group of unidentified assailants", the Congolese Institute for the Conservation of Nature (ICCN) said in a statement.
"Five members of the park's staff have tragically lost their lives," ICCN director general Yves Milan Ngangay said in the statement.
Equipment was also looted and infrastructure suffered extensive damage, he said.
The ICCN, which runs dozens of parks and reserves in the Democratic Republic of Congo, did not mention any claim of responsibility for the attack.
Security forces have restored full control of Upemba park and the Lusinga office, the ICCN said.
Nature parks and reserves in the DRC are often caught up in conflicts over their boundaries and the resources they contain, especially mineral resources.
The ICCN condemned the incursion as a "flagrant violation" of national law and of international conventions protecting natural areas.
It called it a direct breach of the principle of neutrality and non-belligerence governing protecting spaces.
Created in 1939, Upemba park was home to black rhino, elephants, buffaloes, leopards, lions and other endangered species whose populations have since been largely decimated.
In 2021, a warden at the park was killed and three others were injured in an attack.
Lusinga, where Upemba park's headquarters is located, is more than 600 kilometres (370 miles) south of Kivu region, where the Rwanda-backed M23 armed anti-government group has been fighting Congolese armed forces.
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