We use an Earth System model (HadGEM2-ES) to investigate the sensitivity of midnineteenth century tropospheric ozone to vegetation distribution and atmospheric chemistry-vegetation interaction processes. We conduct model experiments to isolate the response of midnineteenth century tropospheric ozone to vegetation cover changes between the 1860s and present day and to CO2-induced changes in isoprene emissions and dry deposition over the same period. Changes in vegetation distribution and CO2 suppression of isoprene emissions between midnineteenth century and present day lead to decreases in global isoprene emissions of 19% and 21%, respectively. This results in increases in surface ozone over the continents of up to 2 ppbv and of 2–6 ppbv in the tropical upper troposphere. The effects of CO2 increases on suppression of isoprene emissions and suppression of dry deposition to vegetation are small compared with the effects of vegetation cover change. Accounting for present-day climate in addition to present-day vegetation cover and atmospheric CO2 concentrations leads to increases in surface ozone concentrations of up to 5 ppbv over the entire northern hemisphere (NH) and of up to 8 ppbv in the NH free troposphere, compared with a midnineteenth century control simulation. Ozone changes are dominated by the following: (1) the role of isoprene as an ozone sink in the low NOx midnineteenth century atmosphere and (2) the redistribution of NOx to remote regions and the free troposphere via PAN (peroxyacetyl nitrate) formed from isoprene oxidation. We estimate a tropospheric ozone radiative forcing of 0.264 W m−2 and a sensitivity in ozone radiative forcing to midnineteenth century to present-day vegetation cover change of −0.012 W m−2.