4,5-Dialkynyl-2-(methyl or phenyl)-3(2H)-pyridazinones (2a-c) were efficiently prepared via Sonogashira cross-coupling reaction on 4,5-dichloro-2-(methyl or phenyl)-3(2H)-pyridazinones (1a,b). Selective Sonogashira reactions were successfully achieved on 4-chloro-2-methyl-5-trifluoromethanesulfonyloxy- (6) and 5-chloro-2-methyl-4-trifluoromethanesulfonyloxy-3(2H)-pyridazinone (11), yielding 5-alkynyl-4-chloro- (7a-c) and 4-alkynyl-5-chloro-2-methyl-3(2H)-pyridazinones (3a,c,e), respectively. Compounds 7a-c and 3a,c,e were subjected to a second Sonogashira reaction giving 4,5-dialkynyl-2-methyl-3(2H)-pyridazinones (8a-c) bearing two different acetylene substituents. Suzuki cross-coupling reaction was also achieved on compounds 7a and 3a producing 4-aryl-5-phenylethynyl- and 5-aryl-4-phenylethynyl-2-methyl-3(2H)-pyridazinones, respectively, in excellent yield.