A new series of pyrimidine and fused pyrimidine derivatives were prepared. These derivatives include 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 pyrimido[4,5-d]pyrimidine systems. The synthetic routes were adopted via formation of substituted amino 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. By consulting the compounds activities, benzylidine and pyrazole parts tethered to the amino pyrimidne ring is the best pharmacophores.