Atmospheric CO2 partial pressure may have been as low as 18 Pa during the Pleistocene and is expected to increase from 35 to 70 Pa before the end of the next century. Low CO2 reduces the growth and reproduction of C3 plants, whereas elevated CO2 often increases growth and reproduction. Plants at high elevation are exposed to reduced CO2 partial pressure and may be better adapted to the low CO2 of the Pleistocene. We examined genotypes of Arabidopsis thaliana from different elevations for variation in growth and reproduction at the CO2 levels of the Pleistocene, the present and the future. Genotypes exhibited limited genetic variation in the response of the production of biomass to changes in CO2, but showed significant variation in reproductive characters. We found evidence that plants from high elevations may be better adapted to low CO2 when considering seed number, which is an important component of fitness. Genotypes showed greater variation in the response of seed number between 35 and 20 Pa CO2 compared to 35 and 70 Pa CO2. We conclude that present-day C3 annuals may have greater potential for evolution in response to the low CO2 of the Pleistocene relative to the elevated CO2 predicted for the future.