Neuropsychiatric systemic lupus erythematosus (NPSLE) can affect both the brain and spinal cord and present with variable neurologic manifestations, including 19 neurologic syndromes according to the ACR (American College of Rheumatology), leading to diverse neurological and psychiatric symptoms ranging from nonspecific symptoms like a headache to devastating symptoms such as seizures and stroke, making NPSLE an important accomplice in morbidity and mortality, which are seen in SLE population. Its management options are still inadequately optimized due to its challenging diversity in presentation, reflecting a range of different pathogenic mechanisms. A better understanding of SLE presentation might improve the present options for managing NPSLE. Here we report a series of five female patients with NPSLE. Out of the five presented cases, four patients have neurological features as an initial manifestation of SLE, which is considered uncommon. The first case of a 50-year-old female patient who had aseptic meningitis presented with headache, back pain, and lower limb weakness associated with numbness after 11 years of being diagnosed with SLE. The second case is of a 20-year-old female patient who had a generalized tonic-clonic seizure with the acute manifestation of hypertensive urgency and posterior reversible encephalopathy syndrome (PRES) as an initial manifestation of SLE. The third case is of a 38-year-old female patient who presented with an acute focal seizure as an initial manifestation of SLE. In the last two cases, a 38-year-old and a 19-year-old female patient presented with an ischemic stroke as the initial manifestation of SLE. On a final note, clinicians should always have SLE in mind as a differential diagnosis when it comes to acute neurological features presenting in any patient with SLE manifestations.