The Israeli airline said that 170 passengers boarded the historic flight, which took three hours and 17 minutes.
The plane took off from Ben Gurion Airport, Israel's international airport outside Tel Aviv, and landed at Dubai International Airport.
Israir added that from now on it would hold 18 weekly flights between the two countries.
Israel's flag carrier El Al announced in November that it will launch a direct passenger flight route to Dubai, with 14 weekly flights starting Dec. 13.
The other leading Israeli airline, Arkia, will also operate direct flights to Dubai, starting Thursday.
Israel and the UAE agreed to formally normalize their relations in mid-August and signed a normalization agreement in the U.S. capital of Washington on Sept. 15.