This work characterizes patterns of temporal variability in surface waters of the central Gulf of Mexico. We examine remote-sensing based observations of sea surface temperature (SST), wind speed, sea surface height anomaly (SSHA), chlorophyll-a concentration (Chl-a) and Net Primary Production (NPP), along with model predictions of mixed layer depth (MLD), to determine seasonal changes and long-term trends in the central Gulf of Mexico between the early 1980s and 2012. Specifically, we examine variability in four quadrants of the Gulf of Mexico (water depth >1000m). All variables show strong seasonality. Chl-a and NPP show positive anomalies in response to short-term increases in wind speed and to cold temperature events. The depth of the mixed layer (MLD) directly and significantly affects primary productivity throughout the region. This relationship is sufficiently robust to enable real-time estimates of MLD based on satellite-based estimates of NPP. Over the past 15–20years, SST, wind speed, and SSHA show a statistically significant, gradual increase. However, Chl-a and NPP show no significant trends over this period. There has also been no trend in the MLD in the Gulf of Mexico interior. The positive long-term trend in wind speed and SST anomalies is consistent with the warming phase of the Atlantic Multidecadal Oscillation (AMO) that started in the mid-90s. This also coincides with a negative trend in the El Niño/Southern Oscillation Multivariate ENSO Index (MEI) related to an increase in the frequency of cooler ENSO events since 1999–2000. The results suggest that over decadal scales, increasing temperature, wind speed, and mesoscale ocean activity have offsetting effects on the MLD. The lack of a trend in MLD anomalies over the past 20years explains the lack of long-term changes in chlorophyll concentration and productivity over this period in the Gulf. Understanding the background of seasonal and long-term variability in these ocean characteristics is important to interpret changes in ocean health due to episodic natural and anthropogenic events and long term climate changes or development activities. With this analysis we provide a baseline against which such changes can be measured