This study of variability in the amount and rate of deformation along the intraplate Reelfoot fault of the New Madrid seismic zone (NMSZ) utilizes diverse research methods, including geophysics, geomorphology, and fluvial sedimentology. The transpressional Reelfoot fault deforms late Holocene Mississippi River sediment into the Tiptonville dome and adjacent Reelfoot basin. Because Reelfoot Lake submerges a portion of the basin, subbottom acoustic profiling of the lake was used to quantify the relief on the uplift. At the natural levee of the abandoned Tiptonville meander, the most appropriate landform along the scarp for measuring cumulative structural relief, a maximum relative vertical uplift of approximately 11.3 m was measured. To identify spatial and temporal variability in surface deformation using geologic methods, we relate fluvial sedimentation to three documented earthquake events during the past 2300 yr (Tuttle et al., 2002, 2005), which is the approximate age of the oldest deformed floodplain sediment (Guccione et al., 2002). Radiocarbon dates from organic material in fluvial and lacustrine sediment indicate that most of the uplift occurred during the last two major seismic events. A minimum of 1.6–3.9 m of uplift was associated with the seismic episode at A.D. 1450±150 and a maximum of 5.9–8.2 m of uplift was associated with the 1812 episode. We estimate a mean short-term uplift rate of 1.2 cm/yr (0.4–2.1 cm/yr with 80% probability) or a mean short-term slip rate of 1.3 cm/yr (0.5–2.3 cm/yr with 80% probability). These values are approximately 2.5 times higher than the long-term rates based on the total amount of uplift averaged over the past 2300 yr (Mueller et al., 1999; Van Arsdale, 2000). Estimating deformation rates associated with individual earthquake recurrences provides information on fluctuating activity of the NMSZ.