Purpose: In this study, we attempted to reduce the negative economic externalities related to Carbon Dioxide (CO2) emissions in the Yangtze River Delta region (YRD) and designed a cross-municipality responsibility-sharing mechanism. Methods: We estimated the municipal CO2 footprints in the YRD from 2000 to 2019 based on nighttime light data and measured CO2 emissions efficiency using a super slack-based measurement (super-SBM) model. Based on this, we designed a scenario of horizontal CO2 compensation among the YRD’s municipalities from the perspectives of both CO2 footprints and CO2 trading (CO2 unit prices in trading were determined based on CO2 emissions efficiency). Results: The results showed the following: (1) The CO2 footprints evolution of the YRD municipalities could be divided into four categories, among which, eleven municipalities showed a decreasing trend. Thirteen municipalities stabilized their CO2 footprints. Thirteen municipalities exhibited strong growth in their CO2 footprints, whereas four municipalities maintained a low level of slow growth. (2) Spatially, CO2 emissions efficiency evolved from a broad distribution of low values to a mosaic distribution of multi-type zones. (3) After 2011, the ratio of CO2 footprint compensation amounts to local Gross Domestic Product (GDP) in most municipalities was less than 0.01%, with its center of gravity shifting cyclically. It was appropriate to start charging the CO2 footprint compensation amounts after 2011, with a dynamic adjustment of 3 years. (4) After 2007, the supply–demand relationship of CO2 trading continued to deteriorate, and it eased in 2016. However, its operational mechanism was still very fragile and highly dependent on a few pioneering municipalities. Innovations: In this study, we designed a horizontal CO2 compensation mechanism from the binary perspective of CO2 footprints and CO2 trading. In this mechanism, the former determines the CO2 footprint compensation amounts paid by each municipality based on whether the CO2 footprint exceeds its CO2 allowance. The latter determines the CO2 trading compensation amounts paid by the purchasing municipalities based on their CO2 emissions efficiency. This system balances equity and efficiency and provides new ideas for horizontal CO2 compensation.