Objective To investigate the epidemiological characteristics, clinical manifestations and laboratory tests of Plasmodium falciparum malaria in Hubei Province from 2020 to 2024, so as to provide insights into prevention of development of severe and fatal cases. Methods Data pertaining to P. falciparum malaria cases reported in Hubei Province from 2020 to 2024 were collected from the National Notifiable Disease Reporting System and the National Parasitic Disease Control Information Management System. The temporal, spatial and population distributions, healthcare-seeking behaviors and laboratory testing of P. falciparum malaria cases were statistically analyzed. Results A total of 251 P. falciparum malaria cases were reported in Hubei Province from 2020 to 2024, including 250 imported cases (99.60%, 250/251) and one case caused by blood transfusion, and 31 severe cases (12.35%, 31/251) and 2 deaths (0.80%). P. falciparum malaria consisted 68.02% (251/369) of all malaria cases, and the proportion of P. falciparum malaria cases in all malaria cases varied in years (χ² = 35.431, P < 0.01). The majority of imported P. falciparum malaria cases acquired infections from Africa (98.80%, 247/250), with the Democratic Republic of Congo (65 cases), Nigeria (46 cases), and Guinea (19 cases) as three largest sources of importation. The largest number of reported P. falciparum malaria cases was found in January, with males aged 31 to 50 years as the predominant demographic. Wuhan City (86 cases), Huangshi City (41 cases), and Yichang City (33 cases) as the three most highly affected cities, and P. falciparum malaria cases were reported in 70.87% (73/103) of counties (districts). The proportion of definitive diagnosis of P. falciparum malaria cases was74.90% (188/251) at initial diagnosis, and lower proportions were observed at village clinics (1/13) and among private practitioners (1/8). The proportions of definitive diagnosis of P. falciparum malaria cases were 73.08% (19/26), 89.22% (91/102), 81.93% (68/83), and 25.00% (10/40) at provincial-, city-, county-, and township and lower-level medical institutions, respectively (χ² = 66.325, P < 0.01). The median interval from disease onset to healthcare seeking was 1 day among P. falciparum malaria cases, with 54.18% (136/251) seeking healthcare services within 1 day of onset and 81.67% (205/251) within 3 days, and the median interval from healthcare seeking to definitive diagnosis was 1 day, with 65.74% (165/251) confirmed within 1 day of seeking healthcare services and 88.45% (222/251) within 3 days. Fever was the most frequent symptom (98.41%, 247/251), and other common symptoms included chills (57.37%, 144/251), sweating (42.23%, 106/251), headache (47.41%, 119/251), and myalgia (10.36%, 26/251). Complications occurred in 16.33% (41/251) of subjects, including severe anemia and liver and kidney injury. The detection rates of P. falciparum malaria were 98.33% (236/240), 95.42% (229/240), and 100% (240/240) in 240 anticoagulant blood samples from P. falciparum cases by rapid diagnostic tests (RDTs), microscopy, and quantitative Real-time PCR assay, respectively (χ² = 12.664, P < 0.05). P. falciparum was identified in peripheral blood smears from 240 P. falciparum malaria cases, with ring-stage alone seen in 70.42% (169/240) of blood smears, rings and trophozoites seen in 20.83% (50/240), and parasites at all developmental stages (rings, trophozoites, schizonts and gametocytes) in 5.00% (12/240). There were 34.17% (82/240) of cases with parasitemias ranging from 1/μL to 100 000/μL, and 21.25% (51/240) with parasitemias of > 250 000/μL. Multivariate logistic regression analysis identified parasitemia was an independent risk factor for severe malaria (OR > 1, P < 0.05). Conclusion A large number of P. falciparum malaria cases with widespread distributions were reported in Hubei Province from 2020 to 2024, and most cases acquired infections in Africa. Fever was the major clinical symptom. Some cases experienced a prolonged duration for a definitive diagnosis, and the proportion of severe case was high among imported P. falciparum malaria cases. Future efforts should focus on improving patients’ awareness of seeking healthcare services, shortening the duration to definitive diagnosis, providing timely and standardized treatment, in order to reduce the development of severe and fatal cases.