A CZE method with two different MS detection conditions (MRM and Full Scan) was developed to determine qualitative and quantitative changes in the metabolic profile of avocado fruits (Persea americana). LODs in MRM approach were found between 20.1 and 203.0 ppb for abscisic acid and perseitol, respectively, whilst in Full Scan, varied within the range 0.22–1.90 ppm for the same metabolites. The RSDs for reproducibility test did not exceed 11.45%. The two MS approaches were used to quantify 10 metabolites (phenolic acids, flavonoids, a carbohydrate, an organic acid, a vitamin and a phytohormone) in 18 samples of avocado at different ripening states, and the achieved results were compared. Perseitol, quinic, chlorogenic, trans-cinnamic, pantothenic and abscisic acids, as well as epicatechin and catechin decreased during the ripening process, whereas ferulic and p-coumaric acids showed the opposite trend. Moreover, some other unknown compounds whose concentration changed largely during ripening were also studied by MS/MS and QTOF MS to get a tentative identification.