The spread of the new coronavirus COVID-19, has led to unparalleled global measures such as lockdown and suspension of all retail, recreation and religious activities during the first months of 2020. Nevertheless, no scientific evidence has been reported so far with regards to the impact on road safety and driving behavior. This paper investigates the effect of COVID-19 on driving behavior and safety indicators captured through a specially developed smartphone application and transmitted to a back-end platform. These indicators are reflected with the spread of COVID-19 and the respective governmental countermeasures in two countries, namely Greece and Kingdom of Saudi Arabia (KSA), which had the most completed routes for users of the smartphone applications. It was shown that reduced traffic volumes due to lockdown, led to a slight increase in speeds by 6–11%, but more importantly to more frequent harsh acceleration and harsh braking events (up to 12%increase) as well mobile phone use (up to 42% increase) during March and April 2020, which were the months where COVID-19 spread was at its peak. On the bright side, accidents in Greece were reduced by 41% during the first month of COVID-19-induced measures and driving in the early morning hours (00:00–05:00) which are considered dangerous dropped by up to 81%. Policymakers should concentrate on establishing new speed limits and ensure larger spaces for cycling and pedestrians in order to enlarge distances between users in order to safeguard both an enhanced level of road safety and the prevention of COVID-19 spread.