Background Malaria is a major health problem in Ethiopia. Sleeping under long-lasting insecticidal nets (LLINs) is its major control strategy. Despite high LLINs use (84%) in Ziway-Dugda District, malaria remained a public health problem, raising concern on its effectiveness. Understanding the effectiveness of malaria control interventions is vital. This study evaluated the effectiveness of LLINs and determinants of malaria in Ziway-Dugda District, Arsi Zone Ethiopia. Methods A matched case–control study was conducted among 284 study participants (71 cases and 213 controls) in Ziway-Dugda District, Arsi Zone, Ethiopia from March to May, 2017. Three health centers were selected randomly, and enrolled individuals newly diagnosed for malaria proportionally. Cases and controls were individuals testing positive and negative for malaria using rapid diagnostic tests. Each case was matched to three controls using the age of (5 years), gender and village of residence. The information was collected using pre-tested structured questionnaires through face to face interviews and observation. Data were entered into Epi-Info version 3.5, and analysed using Stata version-12. Conditional logistic regression was performed, and odds of LLINs use were compared using matched Adjusted Odds Ratio (AOR), 95% confidence interval (CI) and p-value of < 0.05. Results One hundred twenty-three (61.2%) of the controls and 22 (32.8%) of cases had regularly slept under LLINs in the past two weeks. Using multivariate analysis, sleeping under LLINs for the past two weeks (AOR = 0.23, 95%CI = 0.11–0.45); living in houses sprayed with indoor residual spray (IRS) (AOR = 0.23, 95%CI: 0.10–0.52); and staying late outdoors at night in the past two-weeks (AOR = 2.99, 95%CI = 1.44–6.19) were determinant factors. Conclusions Sleeping under LLINs is effective for malaria prevention in the district. IRS and staying late outdoors at night were determinants of malaria. It is recommended to increase attention on strengthening LLINs use and IRS in the area.