A simple and efficient protocol is demonstrated to synthesize medicinally significant new 2-pyridyl/aryl/alkyl substituted 2H-chromenes. The construction of these chromene systems was through a chemoselective Knoevenagel condensation/hemiketalisation process. The reaction afforded a variety of products in good to excellent yields. This methodology has potential applications in the synthesis of biologically and medicinally relevant molecules. For the first time we have synthesized 2-pyridyl/aryl substituted 2H-chromenes in a one-pot reaction.