Abstract Background Little is known about the clinical phenotype of amyotrophic lateral sclerosis (ALS) in non-Caucasian populations. Here, we aimed to describe the clinical characteristics, prognostic factors and survival of Mexican patients with ALS. Methods We conducted a retrospective study by reviewing the medical records of patients with ALS that attended and were regularly followed at a third level hospital in Mexico City from 2000 to 2015. We calculated absolute and relative frequencies of the clinical characteristics from all the participants. We also estimated correlation coefficients between clinical features and overall survival. Additionally, survival rates were compared for all participants grouped according to different clinical features using the Kaplan-Meier method and the log-rank test. Results We enrolled 45 ALS patients, 53.33% had spinal-onset ALS and 46.66% presented bulbar ALS. The male/female ratio was 0.8. The mean age at onset of symptoms was 58.11 years. Mean survival time from onset was 64.73 ± 34.83 months. Cumulative survival rate after 5 years of disease onset was 44.44%. Age at onset and age at diagnosis inversely correlated with overall survival time. Also, we found that bulbar-onset, short diagnostic delay, percutaneous endoscopic gastrostomy, mechanical ventilation, and lower total cholesterol serum levels were associated with short survival. Conclusions The clinical characteristics of Mexican ALS patients differ from the disease phenotype observed in Caucasians. Nonetheless, the predictive value of certain well-recognized prognostic factors remains consistent in our population. The current study provides relevant information for a better understanding of prognostic factors in ALS patients from Mexico and other Latin American countries.