In this work, column-averaged dry-air mole fractions of carbon dioxide (XCO2), methane (XCH4) and carbon monoxide (XCO) are presented for the first time at a mid-latitude urban station, Thessaloniki, Greece, using the Bruker EM27/SUN ground-based low-resolution Fourier Transform spectrometer operated according to the requirements of the Collaborative Carbon Column Observing Network (COCCON). Two years of measurements are presented and examined for seasonal variability. The observed XCO2 levels show the expected seasonal cycle (spring maximum, late summer minimum) with a peak-to-peak amplitude of 12 ppm, with maximum values reported for winter 2021 exceeding 416 ppm. The XCH4 values are shown to increase in the second half of the year, with autumn showing the highest mean value of 1.878 ± 0.01 ppm. The XCO levels, following anthropogenic sources, show high winter and low summer values, exhibiting a rise again in August and September with a maximum value of 114 ± 3 ppb and a minimum in summer 2020 of 76 ± 3 ppb. Additionally, methane and carbon monoxide products obtained from the TROPOspheric Monitoring Instrument (TROPOMI), Sentinel-5P space borne sensor, are compared with the ground-based measurements. We report a good agreement between products. The relative mean bias for methane and carbon monoxide are −0.073 ± 0.647% and 3.064 ± 5.566%, respectively. Furthermore, a 15-day running average is subtracted from the original daily mean values to provide ΔXCO2, ΔXCO and ΔXCH4 residuals, so as to identify local sources at a synoptic scale. ΔXCO and ΔXCO2 show the best correlation in the winter (R2 = 0.898, slope = 0.007) season due to anthropogenic emissions in this period of the year (combustion of fossil fuels or industrial activities), while in summer no correlation is found. ΔXCO and ΔXCH4 variations are similar through both years of measurements and have a very good correlation in all seasons including winter (R2 = 0.804, slope = 1.209). The investigation of the X-gases comparison is of primary importance in order to identify local sources and quantify the impact of these trace gases to the deregulation of earth-climate system balance.