Background <p>Peste des Petits Ruminants (PPR) is a highly contagious viral disease affecting small ruminants with considerable socioeconomic impacts in Ethiopia. Despite its importance, comparative virulence of locally circulating PPR virus strains in indigenous goats remains poorly characterized. This study evaluated six distinct PPRV strains (four lineage-IV, two lineage-III) in experimentally infected Ethiopian goats. Twenty-one Central highland breed goats (12–30&#xa0;months) were randomly allocated into six experimental groups and one control group, with three goats in each group and experimental animals inoculated intranasally (10^4.5 TCID₅₀&#xa0;per ml). Clinical, serological, molecular, and pathogenesis data were collected.</p> Results <p>Five of six strains produced consistent clinical manifestations beginning at 4&#xa0;days post-infection (dpi), with seroconversion by 7 dpi and viral antigens detectable in nasal swabs from 3 dpi. No substantial lineage-specific differences in virulence were observed between lineage-III and lineage-IV strains. One lineage-IV isolate (38,920/19) produced significantly milder clinical manifestations (P &lt; 0.05) and no seroconversion, suggesting potential strain-level variation. Gross and histopathological findings were consistent across virulent strains, with nasal swabs proving most reliable for early diagnosis.</p> Conclusions <p>This first comparative study of Ethiopian PPRV strains establishes similar virulence profiles across lineages in local goats, suggesting that lineage classification alone may not predict clinical outcomes—an important finding for regional disease control strategies. The reduced virulence in one strain suggests factors beyond genomic lineage may influence experimental outcomes, though additional work with standardized protocols is needed to confirm these findings.</p>