The present research aimed to determine the relationship between Jordanian students' 21st century skills (Cs21) and academic achievement in science. The sample of the research consisted of a total of 96 eighth-grade students drawn from four rural and four urban schools in Irbid Qasaba in the governorate of Irbid. Randomly cluster sampling was used to select the sample of the study. To collect data, a Cs21 survey was adapted from the Malaysian Cs21 Instrument (M-21CSI), which was itself based on the enGauge Cs21 framework by Metiri Group and NCREL. The adapted survey was used to measure students' Cs21 and academic achievement in science in the 2015-2016 academic year. The data were analyzed by using descriptive (mean and standard deviation) and inferential statistics (simple linear regression and independent samples t-test). The findings showed that the Cs21 was a significant predictor of the students' academic achievement in science (R = 0.353, p = 0.000). The analysis also showed that urban and female students were better in acquiring the Cs21 than rural and male students. However, their parents' job types had no significant difference in the students' mean scores of Cs21. Therefore, it is recommended that the Cs21 should be integrated into all curricula to improve students' academic achievement and to train future citizens, who are ready for the challenges of the 21st century.