Tobacco bacterial wilt is a destructive soil-borne vascular disease in tobacco production, but the varieties of effective control bactericides are limited at present. Therefore, it is particularly important to explore fungicides with a unique mechanism and excellent control effect. In this study, the sensitivity of tobacco bacterial wilt to five fungicides was determined, the resistance risk of tobacco bacterial wilt to fluazinam was evaluated, and the synergistic toxicities of fluazinam and SYP-14288 with five fungicides (nano-sulfur, nano-copper, nano-silver, benziothiazolinone and kasugamycin) were evaluated by the Wadley method. The results showed that the average EC₅₀ values of fluazinam, SYP-14288, streptomycin, benziothiazolinone and kasugamycin were 1.0840, 0.0378, 0.5463, 2.4299, 9.9273 µg/mL, respectively. The sensitivity baselines of the five fungicides to 40 strains of tobacco bacterial wilt were of normal distribution and presented continuous single peak curves, which could be used for monitoring the resistant strains in fields. The 15 mutants with different resistance levels had strong temperature adaptability and weak pathogenicity. The results of comprehensive evaluation showed that the resistance risk of tobacco bacterial wilt to fluazinam was moderate. The mixtures of fluazinam with benziothiazolinone, kasugamycin, nano-sulfur at the ratio of 1:80, 1:80, 1:40, respectively, had synergistic effects. The synergistic effect of SYP-14288 and nano-sulfur mixture at the ratio of 1:40 was the most obvious. This study provides more alternative fungicides for tobacco bacterial wilt control and a reference for a resistance management strategy.