Urban centers settled under the influence of volcanic activity are common in the Colombian Andes, particularly those such as Manizales city (ca. 400,000 inhabitants) and other smaller towns on the western flank of the Central Cordillera. Several pumice-rich tephra layers widely dispersed beneath the city suggest multiple Plinian-type eruptions have occurred nearby. From this geological record, the four youngest, thickest, and most persistent layers in the region are the most representative of this activity. This work uses mapping, physical descriptions, radiocarbon dating, and calculation of physical parameters to: (1) define and characterize the tephra sequence, (2) determine the age of the eruptions, (3) define the source and eruptive dynamics associated with each of the events, and (4) give insights into the volcanic hazard for Manizales city. The deposits were named in this study as Lower Manizales (Lm), Middle-lower Manizales (Mlm), Middle-upper Manizales (Mum) and Upper Manizales (Um) tephra layers, together forming the “Manizales tephra sequence”. Mapping of the deposits revealed the lower layer originated from the little known Plazuela volcano (~ 15 km east of Manizales), while the others originated in the Cerro Bravo volcano (~ 25 km east of Manizales). The radiometric analysis indicates that the lowest tephra layer originated at 7879.5 ± 55.5 cal. years BP, while the three overlying layers were deposited at 7730 ± 55 cal. years BP, 5294 ± 19 cal. years BP, and 2759 ± 20 cal. years BP. All of these deposits were formed by Plinian-type eruptions, with column heights varying between 18 and 29 km. The minimum tephra volume emitted by each eruption was between 0.21 and 0.38 km3, and the emission rate 21.6 × 107 kg/s for the Lm layer, 3.38 × 107 kg/s for the Mlm layer, 6.27 × 107 kg/s for the Mum layer, and 5.16 × 107 kg/s for the Um layers. The results suggest that the region is strongly threatened by pyroclastic falls associated with several active volcanoes located in the Central Cordillera.