In the present work, the one-pot synthesis of some new 2,4-disubstituted thiazolyl pyrazole derivatives was carried out. The reaction of different pyrazole aldehydes, thiosemicarbazide, and α-halo ketones in one pot afforded the targeted pyrazolyl thiazole derivatives. The synthesis was carried out by following two different methods. The first one is the conventional method in which pyrazole aldehyde, thiosemicarbazide, and α-halo ketones were refluxed in ethanol. In the second method, the reaction mixture was ground at room temperature. The rate of the reaction, the yield of the products, and the purity of the products were compared for both methods. All the synthesized compounds were tested for their antimicrobial activities. It was found that most of the compounds showed good to moderate antibacterial as well as antifungal activities.