Next-generation sequencing deals with exponential growth in sequence databases; the primary challenge is aligning short-read sequences in a time-efficient manner. Despite numerous efforts in contemporary research, they unfortunately face trade-off issues related to time, power consumption, and resource constraints. A hardware accelerator is presented utilizing the Burrows-Wheeler Transformation without involving any sequence terminator to perform short-read sequencing at hardware speed, which eases additional storage, operations, and power consumption. Further, a hardware-based binary search scheme is introduced to reduce power consumption of the accelerator. As an alternative, a parallel searching mechanism is introduced to accomplish the searching operation in a single clock-cycle. The accelerator is evaluated for 64-to-256 nucleotide reference sequences and 32-to-56 nucleotide query sequences. The parallel search scheme consumes ≈11% less time than the binary search-based scheme, consuming ≈1.6–3.7% and ≈4.5–23% more resources and power. While comparing the accelerator with the with-terminator method, it achieves ≈31.01–33.13% gain in processing time, ≈31.28–34.47% saving in hardware resource, ≈33.08–33.29% saving in storage, and ≈14.03–50.79% gain in power consumption. Finally, this accelerator exhibits a gain of ≈52× in throughput without involving any terminator and external memory compared to state-of-the-art architectures.