Hills Quarry Products has submitted a planning application to the county council for a sand and gravel quarry near the village of Clifton Hampden.
It said the development, known as Fullamoor Quarry, will see 2.5m tonnes of earth extracted over 10 years.
But residents said the plan poses a threat "to the health and wellbeing" of their communities.
Chairman of campaign group Bachport (Burcot and Clifton Hampden Protection of the River Thames) Ian Mason said: "It's vital that people express their deep concerns.
"A quarry would devastate a tranquil part of the Oxford Green Belt bordering the Thames and we fear more flooding as the proposed site is in the flood plain."
He added that the biggest concern was the traffic a quarry would generate, with 570 lorry movements a week.
Hills Quarry Products director Peter Andrew said the application followed an 18-month public consultation, which included meetings with residents.
He said: "As a result of the feedback received, we significantly reduced our plans in relation to the volumes of material we hope to extract and the time we will take to work the site.
"The final restoration plans were also scaled back so that no additional material is brought on to site, which in turn reduced the overall number of vehicle movements."
In a statement the company said the proposed quarry covers an area of 104 hectares, of which 76 hectares will be worked.
People have until 13 May to comment on the application.
A campaign group has urged people to object to a quarry they claim would "devastate" Oxfordshire's green belt.