One-pot synthesis of 2-azaflorenones from readily accessed o-bis-ynones through Michael addition, orthogonal aldol reaction, dehydrative isomerization, and a 6-endo-dig-cyclization cascade, triggered by in situ-generated ammonia in the presence of a Cu(I) catalyst, has been discovered and its generality scoped. A few selected reactions of a prototypical 2-azafluorenone have been explored for functionality augmentation in its core structure. Overall, this operationally convenient 2-azafluorenone synthesis involves the formation of five new bonds (3 C-N and 2 C-C) in one pot and embodies many green and sustainable features; notably, the reagent ammonia is subsumed into the reactant o-bis-ynones with atom economy, and the only by-product is water.