The influenza virus is one of the most critical viruses in epidemiology. The 2009 pandemic was caused by a reassortment of the human–avian–swine virus with eight RNA segments responsible for all virus proteins. Segment 7 codifies for matrix proteins M1 and M2. These proteins exhibited low mutation rate because the matrix is fundamental for virion encapsidation and ion channel formation. However, hemagglutinin (HA) segment 4 is one of the most important segments for virulence and hence, is more studied. Brazil had many influenza virus infection cases just before 2009 and from 2011 to 2015, particularly in the Rio Grande do Sul (RS) State. Two hundred samples obtained during the pandemic were used for amplification and sequencing of the viral genome; a total of 19 M and 17 HA amplified segments were sequenced. Sequencing of the M fragment showed that RS has a virus origin different from that in Eastern Asia, Western Europe, USA, and Central America (Mexico and Nicaragua). All the sequences showed amantadine resistance (S31N) and one was out of the phylogenetic tree (Brazil/RS-3335/2009) due to high mutation rate. RS-3335 was the only sample obtained from a patient who died. Many migratory birds that flock to RS are from Europe, Asia, and USA, which could explain this rate of mutation. Insertions and deletions were found in the M1 protein in these samples. The HA sequences showed worldwide spread and less diversity than the M sequences in this study. The most divergent sample was Brazil/RS-3093/2009 that showed mutations in the sialic acid ligation site.