Until now the official tally of endangered plants, compiled by the World Conservation Union, has suggested that only about one in eight plant species could disappear.
But the researchers, writing in the journal Science, now believe this figure to be a gross underestimate.
They say the old assessment does not include a reliable tally of species at risk in the tropical latitudes, where most of the world's plants grow.
Nigel Pitman and Peter Jorgensen say the world is teetering on the edge of an extinction crisis, as more and more plants disappear each year.
The species most at risk live only in small geographic ranges in specific habitats.
The official estimate by the World Conservation Union - the IUCN - suggests that 13% of the world's plant species are under threat, but the two US botanists say it is at least 22% and could be as many as 47%.
They say the IUCN has reliable data for plants in Europe, North America, South Africa and Australia, but there are no reliable figures for tropical, developing countries, where most of the world's plants grow.
In their journal report, the two botanists have taken the trends seen in temperate areas, and extended them to tropical countries.
Their calculations suggest that in the worst case scenario almost half the world's plants are at risk.
It is impossible, however, to establish the exact threat without local research, they argue.
Based on some Ecuadorian work, they estimate the cost of maintaining a global database of threatened plants would cost around $100 per species, per year, for an annual budget of less than $12.1m for all biodiversity "hotspots".
Pitman and Jorgensen tell Science: "Only with the species-by-species information generated by such an undertaking will conservationists be able to monitor and prevent the large-scale plant extinctions foreseen to occur in the tropics in this century."
Nigel Pitman is from the Duke Center for Tropical Conservation, Duke University, North Carolina; Peter Jorgensen is attached to Missouri Botanical Garden in St Louis.