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Abstract Background Iodine deficiency is the major preventable cause of irreversible mental retardation in the world. Ethiopia is a country with high prevalence of iodine deficiency disorders which continue to affect a large number of the country’s population. The aim of the study was to assess the prevalence of iodine deficiency disorder in Wolaita and Dawuro zones. Methods A descriptive, cross-sectional study was conducted in high school and preparatory students in Wolaita and Dawuro zones between April and May 2012. Data were collected from 718 school adolescents using pre-tested questionnaire through systematic random sampling technique. Data were entered and cleaned using Epi-info version 3.5.3 and then transported to SPSS version 20 for analysis. Bivariate and Multivariable logistic regression were done and the cut off value set was P < 0.05 as this is considered as statistically significant. Result The overall prevalence (total goiter rate) of goiter in study area was 351 (48.9%). Students with Grade-1 goiter were 265 (36.9%) while with Grade-2 goiter was 86 (11.9%). Females were by a long way vulnerable for goiter and accounts 60.9% with Pearson correlation coefficient 0.300, P value 0.0001. Generally, the occurrence of goiter in the study area was found to have statistical significant association with sex of respondents (being female) [AOR = 3.526; 95% CI (2.55–4.87)], climatic condition of resident (temperate climate) [AOR = 0.617; 95% CI (0.404–0.943)], frequency of iodized salt use [AOR = 0.484; 95% CI (0.317–0.739)] and consumption of cassava [AOR = 4.184; 95% CI (2.6–6.707)]. Conclusion and recommendation In general, the study revealed that iodine deficiency disorder was a serious public health concern. Nearly half of adolescent students in Wolaita and Dawuro zones were affected by goiter. Therefore, emphasis on a sustainable iodine intervention program targeted at population level, particularly at females is mandatory. Nutrition education along with adequate Universal Salt Iodization program is urgently required.