Ultra-high field 7-Tesla (7 T) MRI has the potential to advance our understanding of neuropsychiatric disorders, including major depressive disorder (MDD). To date, few studies have quantified the advantage of resting state functional MRI (fMRI) at 7 T compared to 3-Tesla (3 T). We conducted a series of experiments that demonstrate the improvement in temporal signal-to-noise ratio (TSNR) of a multi-echo multi-band fMRI protocol with ultra-high field 7 T MRI, compared to a similar protocol using 3 T MRI in healthy controls (HC). We also directly tested the enhancement in ultra-high field 7 T fMRI signal power by examining the ventral tegmental area (VTA), a small midbrain structure that is critical to the expected neuropathology of MDD but difficult to discern with standard 3 T MRI. We demonstrate up to 300% improvement in TSNR and resting state functional connectivity coefficients provided by ultra-high field 7 T fMRI compared to 3 T, indicating enhanced power for detection of functional neural architecture. A multi-echo based acquisition protocol and signal denoising pipeline afforded greater gain in signal power compared to classic acquisition and denoising pipelines. Furthermore, ultra-high field fMRI revealed mood-related neurocircuit disturbances in patients with MDD compared to HC, which were not detectable with 3 T fMRI. Ultra-high field 7 T fMRI may provide an effective tool for studying functional neural architecture relevant to MDD and other neuropsychiatric disorders.