Virulent Newcastle disease virus (vNDV) strains cause Newcastle disease (ND), a highly contagious viral disease of birds with significant economic losses to the global poultry industry. The global spread, constant evolution, varying virulence, and the wide host range of NDV are challenges to the control of ND. Since NDV is an RNA virus that has a high mutation rate, and with the historical precedent of NDV causing panzootics, there is an increased threat of panzootics and the potential for evasion of current diagnostic and control measures. The primary goal of this research was to develop and optimize sequencing protocols for detection and thorough characterization of NDV from different type of clinical samples. Therefore, we aimed to develop a target-independent sequencing protocol to use formalin-fixed paraffin-embedded (FFPE) tissues by using next-generation sequencing (NGS). Multiple complete genomes of NDV were obtained from different types of FFPE tissue samples. These genome sequences were used for enhanced phylogenetic resolution of ND outbreaks. Then we aimed to develop a pan-NDV specific sequencing protocol (AmpSeq) by using MinION Nanopore sequencing technology and a data analysis pipeline for detection, virulence prediction and preliminary pathotyping of NDV. Results demonstrated that this AmpSeq protocol was rapid, sensitive and accurately detected all representative genotypes and sub-genotypes of NDV. Overall, these sequencing protocols will help advance the detection and characterization of NDV isolates and aid in ND control measures worldwide.