Context Fatigue is a particularly common and troubling symptom that has a negative impact on quality of life throughout all phases of treatment and stages of the illness among patients with cancer. Objectives The objective of this meta-analysis is to examine the present status of fatigue prevalence in patients with cancer. Methods The following databases were searched: PubMed, MEDLINE, EMBASE, PsycINFO, Cochrane Library, from inception up to February 2020. Prevalence rates were pooled with meta-analysis using a random-effects model. Heterogeneity was tested using I-squared (I2) statistics. Results A total of 129 studies (N = 71,568) published between 1993 and 2020 met the inclusion criteria. The overall prevalence of fatigue was 49% (34,947 of 71,656 participants, 95% CI = 45–53) with significant heterogeneity between studies (P < 0.000; τ2 = 0.0000; I2 = 98.88%). Subgroup analyses show that the prevalence of fatigue related to type of cancer ranged from 26.2% in patients with gynecological cancer to 56.3% in studies that included mixed types of cancer. In advanced cancer stage patients, the highest prevalence of fatigue (60.6%) was reported. Fatigue prevalence rates were 62% during treatment and 51% during mixed treatment status. The prevalence of fatigue decreased from 64% in studies published from 1996 to 2000 to 43% in studies published from 2016 to 2020. Metaregression identified female gender as a significant moderator for higher prevalence of fatigue, whereas mean age is not associated with fatigue. Conclusion This meta-analysis highlights the importance of developing optimal monitoring strategies to reduce fatigue and improve the quality of life of patients with cancer.