5-Hydroxymethylfurfural (5-HMF) is one of the most significant intermediate platforms for the production of both chemicals and liquid fuel derived from biomass. This study aimed to the assess the efficiency of ultrasound-assisted ionic liquids (ILs)/deep eutectic solvents (DES) in converting fructose to 5-HMF under milder conditions (≤ 100°C). The reaction conditions for the two-step transformation of sugarcane bagasse (SCB) with metal chloride as a catalyst and ultrasonic-assisted DES were optimized. The results showed that under the best conditions for ultrasound-assisted ILs to convert fructose (ultrasonic frequency: 40 kHz, 80°C, 1 h, [Bmim]Cl, D001-cc: 100 mg, fructose addition: 100 mg), the yield of 5-HMF reached 65.29 mol%. In addition, the D001-cc catalyst maintained high catalytic activity after being reused 6 times, and the activated D001-cc basically achieved the initial fructose conversion effect. Under the optimal conditions of ultrasonic-assisted DES fructose conversion (ultrasonic frequency: 40 kHz, 100°C, 30 min, ChCl-OA (molar ratio: 1:2), water addition: 0.46 mL, DES addition: 1 g), the yield of 5-HMF reached 51.87 mol%. Under the best conditions of ultrasonic-assisted DES SCB conversion (ultrasonic frequency: 40 kHz, ultrasonic time: 1 h, DES: ChCl: OA, catalyst: SnCl4·5H2O, water addition: 0.46 mL, 130°C/4 h (150°C/0.5 h)), the yield of 5-HMF reached 47.43 mol%. The study initially showed that ultrasonic-assisted ILs/DES effectively converted fructose in one step. In addition, the synergy of DES and metal chloride can better convert lignocellulosic biomass. Simply stated, the ultrasound-assisted ILs/DES conversion of biomass has realized “physical driving chemistry”. Thus, paving the way of high-value utilization of lignocellulose to become greener and economical.