The demand for noninvasive wearable sensors for on-site monitoring has surged, particularly in the realm of personalized healthcare. This study introduces a pioneering approach employing a MXene-integrated single-stranded carbon yarn-based sensor patch utilizing a minimalist three-thread electrode setup for real-time monitoring of dopamine levels from artificial human sweat. The ability to immediately sew, weave, or stitch sensor platforms onto any type of clothing makes wearable thread-based sensor patches extremely promising and it can be positioned in close proximity to the skin. Flexible conductive carbon yarn (CCY) was modified by Ti3C2Tx MXene by a facile dip-coating method which was used as sensing electrodes. Leveraging MXene’s high surface area and exceptional conductivity, the sensor’s architecture achieved heightened sensitivity and selectivity in dopamine detection and reproducibility in a broad linear range of 1 nM-1 μM with a detection limit of 316 pM, along with real sample tests showing the promise of this platform for real-time physiological monitoring of human performance/fitness under stress as well as diagnostic monitoring through sweat analysis. The three-thread electrode configuration, strategically embedded within the patch, ensures ease of use and comfortable, noninvasive on-body application, offering a promising avenue for continuous, real-time monitoring of dopamine levels in individuals with neurological disorders or relevant medical conditions. This study highlights the potential of MXene-integrated wearable sensor patches with a minimalist electrode setup, advancing the field of wearable sensing technologies for personalized healthcare and point-of-care diagnostics. © 2024 American Chemical Society.