Abstract We report the second extragalactic pulsar wind nebula (PWN) to be detected in the megaelectronvolt–gigaelectronvolt band by the Fermi-LAT, located within the Large Magellanic Cloud. The only other known PWN to emit in the Fermi band outside of the Milky Way is N157B, which lies to the west of the newly detected gamma-ray emission at an angular distance of 4°. Faint, pointlike gamma-ray emission is discovered at the location of the composite supernova remnant (SNR) B0453-685 with a ∼4σ significance with energies ranging from 300 MeV–2 TeV. We present the Fermi-LAT data analysis of the new gamma-ray source, coupled with a detailed multiwavelength investigation to understand the nature of the observed emission. Combining the observed characteristics of the SNR and the physical implications from broadband modeling, we argue it is unlikely that the SNR is responsible for the gamma-ray emission. While the gamma-ray emission is too faint for a pulsation search, we try to distinguish between any pulsar and PWN component of SNR B0453-685 that could be responsible for the observed gamma-ray emission using semi-analytic models. We determine the most likely scenario is that the old PWN (τ ∼ 14,000 yr) within B0453-685 has been impacted by the return of the SNR reverse shock with a possible substantial pulsar component below 5 GeV.