Houses and businesses were destroyed in the deluge on Saturday night that left Las Tejerias, a town about 70 kilometres south-west of the capital Caracas, covered in mud and debris, including felled trees, household items and mangled cars.
"We are seeing very significant damage here, human losses," Venezuelan Vice President Delcy Rodriguez said.
Interior Minister Remigio Ceballos told government television VTV late on Sunday that at least 25 people died in the disaster.
Fifty-two people are missing and about 1,000 have joined the rescue efforts, he said.
Dozens have died in the country in recent months as a result of historically high levels of rain.
"The village is lost. Las Tejerias is lost," said Carmen Melendez, 55, who has lived in the town her whole life.
Residents have dug through the remains of battered homes looking for loved ones, while search teams are using dogs to find survivors trapped in the rubble.
A butcher's shop was among the businesses buried in muddy sediment. It closed because of the Covid-19 pandemic and had been due to reopen on Monday.
"We were waiting for the meat to be shipped in — to start after two years," said Ramon Arvelo, one of the workers helping to remove mud.
Another resident, Loryis Verenzuela, 50, said: "I never thought that something of this magnitude could happen. It's a really big deal."
"We had a huge landslide as a result of the changing climate," said Mr Ceballos, referring to the effects of Hurricane Julia, which passed to the north of Venezuela the night before.
A month's worth of rain fell in one day. "These strong rains saturated the ground," he said.
Images taken by rescue team drones showed huge amounts of earth piled in the streets as residents tried to remove the mud from their houses.
Las Tejerias resident Jose Santiago, 65, held on to an antenna for 40 minutes as the flooding destroyed several houses, including his own.
"The river caught me and I couldn't find anything to do besides climb a roof and grab on to an antenna. I was reborn," he said.
Venezuelan President Nicolas Maduro has declared three days of national mourning for the victims.
People have used social media to offer assistance to the town, which has lost electricity and communication services.
Caracas baseball team Los Leones have called for donations of "non-perishable foods, water and clothes" for the victims.
The landslide, caused by the biggest river flood in the area in 30 years, is the worst in Venezuela this year.
In August, at least 15 people died in the Venezuelan Andes after heavy rain caused mud and rock slides.
A month later, at least eight people died when floods hit a religious retreat in the western part of the country.
In 1999, landslides killed about 10,000 people in the state of Vargas, north of Caracas.