Acute lower limb ischemia (ALLI) is a common vascular emergency. However, ALLI presenting as the initial symptom of acute leukemia (AL) is scarce. Here we present a case of ALLI in the setting of acute myeloid leukemia (AML) while systematically reviewing the current literature to withdraw conclusions about the management, prognosis, and treatment for this atypical presentation of AL. We conducted a systematic electronic research according to Preferred Reporting Items for Systematic Review and Meta-Analysis protocol (PRISMA) for articles published from January 1981 up to January 2021 concerning ALLI in the setting of acute leukemia (AL). Patients' baseline characteristics were recorded and nine outcomes of interest were studied. Twenty-six individuals, 16 males with a mean age of 46.3 years (±20) were included in this review. The diagnosis included 13 AML patients (50%), 11 acute promyelotic leukemia (APL) (42.3%) and two acute lymphoblastic leukemias (ALL) (7.7%). Treatment varied among nine different regimens. Four patients were treated with chemotherapy alone (15.4%), four with thrombectomy alone (15.4%), and 11 with a combination of chemotherapy and thrombectomy (42.3%). Eight major amputations were recorded (30. 8%). Thirty-day mortality was 35.7%. Forty-eight peripheral thrombotic events were recorded with 12 patients suffering recurrent thrombotic events. ALLI as the presenting symptom of AL is a rare condition that carries significant mortality and amputation rates. Timely diagnosis is crucial concerning short-term survival and limb salvage. APL, despite being the rarest form of AL, represented a significant proportion of the patient population in this review. The role of leukostasis in the disease's progression and the efficacy of leukapheresis as a treatment regimen should be further investigated through case-control studies.