A new series of pyrimidines and fused pyrimidines derivatives including differently substituted benzylidenes, heterocycles such as pyrazole ring and fused ring systems such as triazolo [4,3-a] pyrimidine, pyrido [2,3-d] pyrimidine and pyramido [4,5-d] pyrimidine systems is reported. The synthetic routes were adopted via formation of substituted pyrimidine core structure in simple and efficient procedures. The chemical structures of new compounds were fully characterized by using complete spectral analyses data. The new compounds were evaluated for their anti-cancer and antimicrobial activities. Among the tested compounds, compounds 7i, 7h and 11c exhibited the best activity against different cancer cell lines. Compounds 8c, 11c and 14b showed potent activity as anti-microbial agents compared to standard drugs.