For several years, fish smoking has been the widely adopted processing method among artisanal fish smokers located along the coastal zones in many parts of West Africa including Ghana. However, several issues pertaining to biochemical and microbiological contaminants still remain, mainly because of the suboptimal, unhygienic fish handling during the processing. To help curtail the problem, we developed and implemented a simple good manufacturing practice (GMP) system for experimentation at two local fish smoking facilities (Facility A, FA; Facility B, FB) to assess the effectiveness for improving the quality of smoked fish. The implementation of GMP did not affect the physical properties of the smoked fish but improved the peroxide value, total volatile base nitrogen, polyaromantic hydrocarbons and histamine levels. The total aerobic counts decreased from 3.96 ± 0.12 cfu/g to 1.52 ± 0.28 cfu/g (FA) or from 4.10 ± 0.2 cfu/g to 1.85 ± 0.85 cfu/g, (FB). The coliforms and Escherichia coli decreased respectively from 1.69 ± 0.12 cfu/g and 1.15 ± 0.21 cfu/g (FA) and from 1.74 ± 0.37 cfu/g and 1.24 ± 0.37 cfu/g, (FB) to below detection (no observed colony) after introducing the single use of potable water, use of smoking oven and fish core temperature of 108.1 ± 7.5 °C and 82.5 ± 3.9 °C, respectively for 2 h, wearing of safety apparels, drying and cooling of smoked fish under nets, and the use of waste disposal bins. The results show that sensitization and training of fish smokers in GMP may be relevant for improving the microbial and overall quality of smoked fish.