Lake Karla (Central Greece) is a unique example - at European scale - of a shallow lake ecosystem that was dried in the 1960s and in 2009 started to be restored. The lake is listed in the network of the Greek protected areas as it is considered a vital aquatic ecosystem, in terms of biodiversity. It has, however, already been adversely affected by both agricultural and industrial land uses in the surrounding area, leading to eutrophication and shifting algal community towards bloom-forming toxic cyanobacterial species. After repeated heavy-blooms, cyanotoxin occurrence and mass fish kills, the local ecosystem management authority has implemented a water quality monitoring program (July 2013 - July 2015) to assess environmental pressures and the response of aquatic biota in the lake. Microscopic, immunological, and molecular techniques combined with physico-chemical parameters, complemented by liquid chromatography tandem mass spectrometry (LC-MS/MS), were used to monitor cyanobacteria blooms and the associated cyanotoxin production from three different sites in Lake Karla and from the adjacent Kalamaki Reservoir. Water quality was also assessed by the structure of benthic invertebrate community on the sediment. Cyanobacteria were the main phytoplankton component, representing more than 70% of the total phytoplankton abundance; dominant taxa belonged to Cylindrospermopsis raciborskii, Limnothrix redekei, Anabaenopsis elenkinii, and Microcystis spp. Euglenophytes (Euglena), diatoms (Nitzschia), and chlorophytes (Scenedesmus) were also important phytoplankton constituents. LC-MS/MS confirmed the co-occurrence of microcystins, cylindrospermopsin, saxitoxin, neo-saxitoxin and anatoxin-a. The occurrence of cyanotoxins in relation to the persistent and dominant cyanobacteria and the impact of cyanobacterial harmful algal blooms on the newly constructed lake along with the land uses and the emergent mitigation measures are discussed.