The fatigue life prediction of steel bridges depends on the amplitude, stress ratio, stress interaction (stress order), and frequency of variable stress spectra. The stress interaction is always altering the crack growth rate under the application of variable stress spectra. The random nature of variable stress spectra makes it difficult to model all these influential parameters correctly. In this study, the fatigue prediction model of steel bridges based on linear elastic fracture mechanics was developed by using measured variable stress spectra of three steel bridges. Variable stress spectra data are used to calculate and analyze the entropy index of stress interaction and crack severity index (CSI) of the effective stress associated with the characteristics of the variable stress spectra. Using these results, the results of fatigue analysis, and multiple regression, we develop prediction models for entropy index-CSI-fatigue crack length, average daily truck traffic (ADTT)-CSI-fatigue crack length, and ADTT-entropy-fatigue crack length. These models can predict the fatigue life of a bridge structure, and this information can be used to plan lifetime maintenance for similar bridges with variable stress spectra.