The conventional gold nanoparticles (AuNPs) with insufficient brightness face substantial challenges in developing a sensitive lateral flow immunoassay (LFIA). Herein, multibranched manganese–gold (Mn–Au) nanoparticles (MnAuNPs) with a Au core–Mn shell nanostructure were synthesized by a one-pot method. The Mn shell of valence-rich and Au core of high electron transfer efficiency endowed MnAuNPs with oxidase-like activity, which oxidized 3,3′,5,5′-tetramethylbenzidine (TMB) only by electron transfer. Ox-TMB, which was the oxidation product of TMB, is an excellent photothermal agent. Furthermore, the synergistic photothermal effect of ox-TMB and MnAuNPs significantly enhanced the photothermal conversion efficiency. The synergistic photothermal effect of multibranched MnAuNPs and ox-TMB has enabled highly sensitive quantitative detection. The LFIA based on MnAuNPs (cascade LFIA) has achieved sensitive detection of Escherichia coli O157:H7. The entire detection process was completed in 25 min. The limit of detection of cascade LFIA was 239 CFU mL–1, which was 37.21-fold lower than that of AuNPs-LFIA (8892 CFU mL–1). The recoveries of cascade LFIA were 82.63–111.67%, with coefficients of variation of 4.28–14.19%. Overall, this work suggests the potential of MnAuNPs and ox-TMB in the development of sensitive LFIA and broadens the biosensing strategies for point-of-care testing.