Depression is a common problem with debilitating effects. Both negative interpretation biases and rumination are related to depression, but how these factors interact to produce depression is unclear. Prior cross-sectional research indicates that negative interpretation biases have an indirect effect on depression symptoms through rumination, but to date, no longitudinal studies have examined this indirect effect, and prior studies have not differentiated between rumination subtypes. To examine these questions, data were collected online at three time points from undergraduates. Simple mediational models examined whether negative interpretation bias had an indirect effect on depression symptoms through rumination and rumination subtypes (brooding and reflection), and reverse models examined direction of effects. Cross-sectional analysis supported prior findings that interpretation bias had an indirect effect on depression symptoms through rumination, β = −.19, 95%CI [−.23, −.14], through both brooding, β = −.14, 95%CI [−.18, −.10], and reflection subtypes, β = −.09, 95%CI [−.12, −.05]. However, longitudinal analyses found no indirect effects of interpretation bias on depression symptoms through rumination, β = −.02, 95%CI [−.07, .02]; brooding: β = −.02, 95%CI [−.06, .01], reflection: β = .01, 95%CI [−.02, .04]. These longitudinal results contradict findings that cognitive biases lead to depression symptoms through rumination. The complex interplay between cognitive biases, rumination, and depression remains an important direction for future research.