Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is the leading cause of bacteremia and meningitis in neonates; however, it also causes meningitis in adults, although much less frequently. After the detection of penicillin-non-susceptible GBS (PRGBS) for the first time in 2008 by Japanese researchers, clinical PRGBS isolates have been reported worldwide. These isolates need to be given due attention for being non-susceptible to multiple drugs. Herein, we present the first clinical report of meningitis caused by PRGBS. A 41-year-old Japanese male receiving an immunosuppressant visited hospital complaining of fever. Although he did not have meningitis-related symptoms or physical findings, determination of the cause of fever by Gram-staining of the spinal fluid revealed gram-positive cocci in pairs and chains. Initially, he was hospitalized on the diagnosis of cerebral meningitis caused by Streptococcus pneumoniae. However, culture of the spinal fluid revealed the β-hemolytic colonies on blood agar. Biochemical testing and mass spectrometry revealed the isolated organism as GBS (serotype Ib). The minimum inhibitory concentration (MIC) of penicillin G for the isolated strain was 0.5 μg/mL, which is greater than the MIC criteria for "susceptibility" to penicillin G for beta-hemolytic streptococci according to Clinical and Laboratory Standards Institute standards. The isolated strain was also resistant to macrolide (MIC ≥ 8 μg/mL) and fluoroquinolone (MIC ≥ 8 μg/mL). The patient recovered without neurologic sequelae upon treatment with ceftriaxone, vancomycin, and corticosteroids for 4 days, and subsequently with ampicillin for 17 days. The rate of isolation of PRGBS in the clinics has gradually increased, particularly in Japan. Although PRGBS isolated in the present case was susceptible to ampicillin and cephalosporins, strains not susceptible to ampicillin, cefotaxime, and ceftriaxone have already been isolated, indicating the prospects for limited range of effective antibiotics against PRGBS infections, including meningitis, in the near future.