Sex workers are commonly claimed to be at heightened risk of fatal victimization. Although prior research indicates that the dynamics of sex worker homicides resemble sexual homicides more than nonsexual homicides, little is known about how these types of homicides compare in terms of offending patterns. This study considers a sample of 2,851 single‐victim, single‐offender homicide cases extracted from a 37‐year (1976–2012) US Supplementary Homicide Reports database, and compares the offender, victim, and offender characteristics of 243 sex worker homicides (189 males and 54 females) with those of 2608 sexual homicides (2474 males and 134 females). The findings suggest that the offender, victim, and offense characteristics of general, male‐offender, and female‐offender sex worker homicides are essentially different from the characteristics of sexual homicides. Logistic regressions further indicate that most offender, victim, and offense characteristics on the occurrence of general and male‐offender sex worker homicides were significantly associated with the perpetration of general and male‐offender sex worker homicides, with reference to sexual homicides. These findings offer insights relevant to the prioritization of criminal investigative practices.