The continued use of fossil fuels in internal combustion engines (ICEs) and the increasing number of active vehicles contribute to a range of problems, including environmental footprint, global warming, environmental issues, and threats to human health. Therefore, it is essential to identify and utilize alternative fuels that can replace fossil-based fuels in ICEs. In this study, long-chain amyl alcohol, a by-product of ethanol production (considered waste), is used as an alternative fuel in a spark-ignition (SI) engine. This study addresses the lack of research on the combined effects of compression ratio (CR) variation and titanium dioxide (TiO<inf>2</inf>)-assisted 2-propanol use in waste-derived amyl alcohol–gasoline blends in SI engines, particularly from thermodynamic and environmental impact perspectives. In the experimental study, the effects of CR and TiO<inf>2</inf> nanofluid usage on performance, emissions, energy, exergy, sustainability, environmental and enviroeconomic impact are investigated in an SI engine operating with a gasoline/amyl alcohol blend. In the study, 20 % amyl alcohol (A20) by volume is used in gasoline, while TiO<inf>2</inf> nanofluid is used at 5 ml (A20Ti5) and 10 ml (A20Ti10) per liter, respectively. Among the experimental operating parameters, the engine torque changes from 1 Nm to 4 Nm (four different loads), while the CR changes from 7:1 to 8.5:1 (two different CRs). The best overall results are generally achieved with the A20Ti10 fuel. Under high CR conditions, the A20Ti10 fuel reduces specific fuel consumption by an average of 15.5 % and increases thermal efficiency by an average of 21.9 %. A maximum reduction of 24 % in exergy destruction (at 1 Nm) and a maximum improvement of 29.7 % in exergy efficiency (at 1 Nm) are observed. Additionally, under low CR conditions, the total environmental impact decreases by an average of 5.5 % (with A20Ti5 fuel), while increasing the CR adversely affects the environmental impact. Conversely, the enviroeconomic impact shows an average reduction of 24 % under high CR conditions (with A20Ti10 fuel).