Developing high-performance sensing materials for the sensitive detection of methylmalonic acid (MMA) in biological samples is pretty important for the early diagnosis, recognition and treatment of related diseases. In this work, a Co(II)-based metal–organic framework (MOF), {[Co(L)(bibp)]bibp·2H₂O}_n (1) (H₂L = 2,6-di(4-carboxylphenyl)-4-(4-(triazol-1-ylphenyl))pyridine, and bibp = 4,4′-bis(imidazolyl)biphenyl), has been solvothermally obtained with good chemical and thermal stabilities. Concurrently, 1 showed an excellent fluorescence turn-on response capability for the detection of the vitamin B₁₂ biomarker MMA with outstanding sensitivity, selectivity, recoverability and anti-interference ability, which makes it the first Co(II)-based MOF as a turn-on fluorescence sensor for MMA. Moreover, a mechanism study showed that photoinduced electron transfer is crucial to MMA detection.