The estimates of anthropogenic CO2 emissions in the megacity of St. Petersburg per square kilometer and for the entire area of the city (integral emissions), obtained on the basis of ground-based measurements of the CO2 content within the city limits, are presented. To determine emissions, the inverse problem was solved using the results of comparison between the measured and calculated data (ODIAC dataset) of the anthropogenic contribution to the CO2 content from the city. Two approaches were applied. In the first, the tomographic method was used and the anthropogenic emissions of three city districts per square kilometer were determined. In the second, all available measurements were used to find the average correction factor R and estimates of the integral CO2 emissions of the entire megacity and its central part. The emissions per square kilometer for the south of the city are in the range of 32.7–48.3 kt/km2 year; for the center, 69.0–97.5 kt/km2 year; and for the north, 78.2 kt/km2 year. The integral CO2 emissions from the central part and the entire metropolis are 39.8 and 65.3 Mt/year, respectively. Inaccuracies in the estimate reach 20–40%. The estimates of the CO2 anthropogenic emissions in St. Petersburg are higher by approximately two times than earlier results.