Perfluorooctanoic acid (PFOA) is persistent in environment due to its stable structure. It is also toxic to animals and human. The objective of this research is to remove PFOA with a non-thermal plasma reactor, anaerobic and aerobic bio-reactors, and their combination. Mineralization and defluorination (i.e., fluoride production) occurred in the plasma reactor. Neither PFOA removal nor fluoride production was observed in the bioreactors. In the plasma reactor with Argon as the carrier gas, 20 µM of PFOA in deionized (DI) water was removed to 4.22 and 4.04 µM, respectively, when the hydraulic retention time (HRT) was 0.21 s and 0.15 s, respectively. When the carrier gas was changed to Helium, PFOA was removed to 3.85 µM and 3.77 µM, respectively. Therefore, the carrier gas and HRT did not have significant effect on PFOA degradation. However, the carrier gas and HRT strongly affected the defluorination rate: 11% (for HRT = 0.21 s) and 6.5% (for HRT = 0.15) when Argon was the carrier gas, and 22% (for HRT = 0.21 s) and 8.6% (for HRT = 0.15 s) when Helium was the carrier gas. Consequently, a higher energy yield was achieved with Helium as the carrier gas (maximum of 11.3 × 10⁻¹¹ mole F- production/J) than with Argon as the carrier gas (maximum of 6.43 × 10⁻¹¹ mole F- production/J). Perfluoroheptanoic acid (PFHpA) and perfluorohexanoic acid (PFHxA) were observed in the effluent of the non-thermal plasma reactor by using liquid chromatography-tandem mass spectrometry (LC/MS/MS). The intermediates production rate was higher when argon was the carrier gas compared with Helium, probably because the degradation mechanisms are different for PFOA and their intermediates.