Fish are vital for food security and economic growth, but their perishable nature leads to significant quality deterioration and post-harvest loss. Additionally, improper handling and aquatic pollution can increase microbial and heavy metal contamination, posing health risks. Although salting extends shelf life and enhances flavor, the lack of standardized practices raises concerns about the quality of salted products. In Lake Tana, inadequate handling and processing of fish are reported, but data on fish proximate composition, microbial quality, heavy metal contamination, salt levels, and fishers’ knowledge, attitudes, and practices towards the safety of fish products and post harvest losses remain limited. Thus, this study was designed to address these gaps. Data were collected through laboratory analyses (proximate composition, microbial quality, and heavy metal levels), experimental studies, field observations and interviews. For microbial and proximate analyses, 75 fish samples (45 raw, 30 sun-dried) were collected from Bahir Dar, Mitsrihaba, and Gorgora sites. For heavy metal analyses, 15 equal-sized individual samples of Oreochromis niloticus were collected. To investigate the effect of different salt concentrations on fish quality, 18 kg of Labeobarbus spp. were subjected to dry salting at 10%, 20%, and 30% concentrations. To evaluate the level of fishers’ knowledge, attitudes, and practices regarding the safety of fish products, as well as to assess post-harvest losses, six fish landing sites (Bahir Dar, Nabega, Mitsrihaba, Gorgora, Delgi, and Kunzla) were selected. A total of 344 fishers were randomly interviewed at the landing sites. Proximate of fish samples revealed that sun-dried Clarias gariepinus and Labeobarbus spp. had significantly higher contents of ash, fat, protein, carbohydrates, energy, and salt compared to their raw forms. Microbial analysis showed that a significant differences (p < 0.05) in the counts of aerobic mesophilic bacteria, Staphylococcus aureus, yeast, and mold between raw and sun-dried samples. Higher counts of S. aureus, yeast, and mold were observed in the sun-dried samples, whereas aerobic mesophilic load was high in the raw Labeobarbus spp., C. gariepinus and Oreochromis niloticus samples. Additionally, total and fecal coliform counts showed significant variation between raw and sun-dried fish, with higher levels observed in the raw samples. While sun-dried samples had lower fecal coliform levels, 33.33% of dried Labeobarbus spp. and 46.67% of dried C. gariepinus still exceeded the limit. Salmonella spp. and Shigella spp. were also isolated from both raw and dry fish samples. The Pearson correlation analysis showed a strong positive correlation between water activity and vi microbial load (r = 0.756, p < 0.05), as well as between moisture content and microbial load (r = 0.786, p < 0.05). Heavy metal analysis of Oreochromis niloticus muscle tissue revealed concentrations of 0.165 mg/kg for chromium, 0.085 mg/kg for arsenic, 0.054 mg/kg for lead, and 0.010 mg/kg for cadmium. Except for chromium, the concentrations of the assessed metals were below the maximum permissible limits. The experimental study showed that both the moisture and ash content of dry-salted Labeobarbus spp. significantly changed as salt concentration increased from 10% to 30%, with ash content increasing and moisture content decreasing. However, no significant changes in fat and protein content were observed between the 20% and 30% salt treatments. The aerobic mesophilic bacteria count was 3.06 log CFU/g at 30% salt, lower than at 10% and 20%. Sensory scores for 10% salt-treated Labeobarbus spp. significantly differed from those of the 20% and 30% treatments in all attributes except color (p < 0.05). Post-harvest loss assessments revealed an annual loss of 6.32% for raw fish and 11.32% for sun-dried fish. Main causes contributing to these losses included delays in net hauling, poor handling practices, and limited market access for sun-dried fish. Although fishers showed good knowledge and positive attitudes toward safety of fish products, their actual practices remain inadequate, highlighting a gap between awareness and implementation. Therefore, it is essential to improve fishers’ handling practices, identify sources of contamination, and implement effective waste management systems to enhance fish quality and safety.