To flexibly update behavior in response to a sudden change in outcome of previously learned cues and actions, neural activity in the orbitofrontal cortex (OFC) must be updated. Novelty activates the locus coeruleus (LC), a group of cells in the brainstem that release the neurotransmitter norepinephrine (NE) throughout the brain. NE release may drive behavioral flexibility by facilitating the reorganization of neural activity in target brain areas, including the OFC. To test this hypothesis, mice were assessed in a T-maze reversal learning task, which requires subjects to reverse a previously learned strategy to succeed. During this task, neural activity in the OFC was recorded via miniendoscopic calcium imaging, which allows us to observe populations of neurons over multiple days. During reversal, the LC was either excited or inhibited using chemogenetic, pharmacological, or optogenetic manipulation. We find an inverse-U-shaped effect of NE on behavioral flexibility, with a sustained increase or decrease in LC activity during the task decreasing reversal performance. In the OFC, we observe that different patterns of neural activity underlie behavioral deficits caused by too little or too much NE. Inhibiting the LC impairs reorganization of OFC neural activity, with a higher proportion of cells continuing to respond to the previously rewarded side of the maze. Exciting the LC increases the proportion of OFC cells responding to both sides of the maze, potentially decreasing the signal to noise ratio of the system. These experiments investigate an important brain circuit from the level of individual cells to modulation of behavior. The study provides important insights into population-level OFC neural activity during learning and reversal and how LC-mediated NE signaling modulates this OFC activity and reversal learning. The knowledge gained through this study may also provide scientific rationale for targeting circuit-specific deficits in neurological disorders where behavioral flexibility is impaired.