In the unprecedented year of 2020, the rapid spread of COVID-19 disrupted everyday activities worldwide, leading the majority of countries to impose lockdowns and confine citizens in order to minimize the exponential increase in cases and casualties. To date, very few studies have been concerned with the effect of the pandemic on driving behavior and road safety, and usually explore data from a limited time span. Method: This study presents a descriptive overview of several driving behavior indicators as well as road crash data in correlation with the strictness of response measures in Greece and the Kingdom of Saudi Arabia (KSA). A k-means clustering approach was also employed to detect meaningful patterns. Results: Results indicated that during the lockdown periods, speeds were increased by up to 6%, while harsh events were increased by about 35% in the two countries, compared to the period after the confinement. However, the imposition of another lockdown did not cause radical changes in Greek driving behavior during the late months of 2020. Finally, the clustering algorithm identified a “baseline,” a “restrictions,” and a “lockdown” driving behavior cluster, and it was shown that harsh braking frequency was the most distinctive factor. Policy recommendations: Based on these findings, policymakers should focus on the reduction and enforcement of speed limits, especially within urban areas, as well as the incorporation of active travelers in the current transport infrastructure.