Mugabe addressed thousands of supporters outside the headquarters of the ruling ZANU-PF party, issuing a clear threat to Evan Mawarire, the pastor who has become the figurehead of a new opposition movement.
"The Mawarires. I want to warn them very strongly," Mugabe said in a fiery 45-minute speech.
"ZANU-PF will not tolerate any nonsense.
"Once you begin to interfere with our politics, you are courting real trouble.
"We know how to deal with our enemies who have been trying to bring about regime change."
But a wave of street demonstrations and strikes has shaken his government, which has run out of money and is struggling to pay its soldiers and civil servants.
In the latest sign of growing national instability, veterans of Zimbabwe's independence war, who have previously been loyal supporters of the president, issued a statement last week denouncing him.
"When we find out who the people were, the party will discipline them. The punishment will be severe," Mugabe said in his first comments on the veterans' criticisms.
Mugabe today also repeated his accusations that western countries were fuelling opposition against him.
"The foreign embassies in the country that are interfering with our politics... I want to warn them to desist from it," he said.
"(They) try and subvert our system of government."
Authorities in Zimbabwe have alleged the French and US envoys support the popular "ThisFlag" protest movement, named after the hashtag first adopted by Mawarire.
Mugabe's audience today was made up of party loyalists, many of them waving the party flag and wearing party regalia displaying his portrait.
